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Peng Y, Long XD. The role of the ceRNA network mediated by lncRNA SNHG3 in the progression of cancer. Discov Oncol 2024; 15:514. [PMID: 39349640 PMCID: PMC11442963 DOI: 10.1007/s12672-024-01184-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 07/22/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) are a distinct class of RNAs with longer than 200 base pairs that are not translated into proteins. Small Nucleolar RNA Host Gene 3 (SNHG3) is a lncRNA and frequently dysregulated in various human cancers. OBJECTIVE This review provides a comprehensive analysis of current research on lncRNA SNHG3, focusing on its role within the competitive endogenous RNA (ceRNA) network and its implications in cancer. METHODS A systematic literature review was conducted using PubMed up to October 2023. The search strategy included keywords such as "lncRNA SNHG3", "competitive endogenous RNA", "cancer", and related terms. Studies were selected based on relevance to SNHG3's involvement in cancer pathogenesis and progression. RESULTS Disruptions in the ceRNA network involving lncRNA SNHG3 can impair normal cell growth and differentiation, significantly contributing to disease pathogenesis, particularly cancer. This review highlights SNHG3's substantial impact on various cancer processes and its potential as a diagnostic and therapeutic tool for aggressive cancers. CONCLUSION The findings underscore SNHG3's pivotal role in cancer prevention, diagnosis, and treatment, laying a foundation for future research in cancer management. Insights from this review emphasize the necessity for further exploration and development of SNHG3-based diagnostic and therapeutic strategies.
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Affiliation(s)
- Ying Peng
- Department of Pathology, the First Affiliated Hospital, Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
- Department of Pathology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, 518000, Guangdong, People's Republic of China
- Department of Pathology, the Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi Zhuang Autonomous Region, Baise, 533000, People's Republic of China
| | - Xi-Dai Long
- Department of Pathology, the Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi Zhuang Autonomous Region, Baise, 533000, People's Republic of China.
- Department of Tumor Pathology, Key Laboratory of Tumor Molecular Pathology of Guangxi Higher Education Institutes, Guangxi Zhuang Autonomous Region, Baise, 533000, China.
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Soltani Khaboushan A, Salimian SN, Mehraban S, Bahramy A, Zafari N, Kajbafzadeh AM, Johnson J, Majidi Zolbin M. Prognostic significance of non-coding RNAs related to the tumorigenic epithelial-mesenchymal transition (EMT) process among ovarian cancer patients: A systematic review and meta-analysis. Heliyon 2024; 10:e35202. [PMID: 39253159 PMCID: PMC11382180 DOI: 10.1016/j.heliyon.2024.e35202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 07/22/2024] [Accepted: 07/24/2024] [Indexed: 09/11/2024] Open
Abstract
Introduction Ovarian cancer is the seventh most prevalent cancer among women. It has high mortality and morbidity and imposes a great burden on healthcare systems worldwide. Unraveling the mechanisms behind the Epithelial-Mesenchymal Transition and finding a panel for predicting the prognosis of the disease may help find the appropriate treatment approaches for the management of the disease. The overarching aim of this systematic review was to define a panel of different types of EMT-associated non-coding RNAs (ncRNAs) with significant prognostic value in all types of ovarian cancers. Methods We searched PubMed, Web of Science, Scopus, and Embase till Jun 2024 to retrieve relevant papers. Two independent reviewers screened papers, and discrepancies were resolved by consensus. Publications related to the dysregulation of different types of ncRNAs, including microRNAs, lncRNAs, and circRNAs, only in patients with ovarian cancer were included. The participation of ncRNAs in epithelial-mesenchymal transformation should be assessed via methods evaluating different EMT-related proteins. To assess the quality and risk of bias for the included case-control and cohort studies, refined Newcastle-Ottawa Scale (NOS) and Quadas-2 were recruited. A bivariate meta-analysis was performed to analyze extracted data. Results A total of 37 studies with overall 42 non-coding RNAs (15 microRNA, 24 long non-coding RNAs, and 3 circular RNAs) were entered into the analysis. Overall diagnostic odds ratio for ncRNAs in lymph node metastasis, distant metastasis, TNM stage, and clinical stage were 4.19, 3.80, 6.52, and 3.97, respectively. Also, a hazard ratio of 1.39 (P = 0.32) for overall survival was observed. Bioinformatic analyses on the Pan-cancer database demonstrated a significant correlation between low expression of miRNA and high expression of lncRNAs with poor prognosis of ovarian cancer. Conclusion Based on the results, the defined panel of ncRNAs can properly predict prognostic factors related to EMT in ovarian cancer without involving potentially invasive methods.
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Affiliation(s)
- Alireza Soltani Khaboushan
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyedeh Nazanin Salimian
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Saghar Mehraban
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Afshin Bahramy
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Narges Zafari
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdol-Mohammad Kajbafzadeh
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Joshua Johnson
- Division of Reproductive Sciences, Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA
| | - Masoumeh Majidi Zolbin
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
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Zhao J, Li G, Zhao G, Wang W, Shen Z, Yang Y, Huang Y, Ye L. Prognostic signature of lipid metabolism associated LncRNAs predict prognosis and treatment of lung adenocarcinoma. Front Oncol 2022; 12:986367. [PMID: 36387240 PMCID: PMC9664164 DOI: 10.3389/fonc.2022.986367] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 10/17/2022] [Indexed: 07/25/2023] Open
Abstract
BACKGROUND Lung adenocarcinoma (LUAD) is the most predominant histological subtype of lung cancer. Abnormal lipid metabolism is closely related to the development of LUAD. LncRNAs are involved in the regulation of various lipid metabolism-related genes in various cancer cells including LUAD. Here, we aimed to identify lipid metabolism-related lncRNAs associated with LUAD prognosis and to propose a new prognostic signature. METHODS First, differentially expressed lncRNAs (DE-lncRNAs) from the TCGA-LUAD and the GSE31210 dataset were identified. Then the correlation analysis between DE-lncRNAs and lipid metabolism genes was performed to screen lipid metabolism-related lncRNAs. Cox regression analyses were performed in the training set to establish a prognostic model and the model was validated in the testing set and the validation set. Moreover, The role of this model in the underlying molecular mechanisms, immunotherapy, and chemotherapeutic drug sensitivity analysis was predicted by methods such as Gene Set Enrichment Analysis, immune infiltration, tumor mutational burden (TMB), neoantigen, Tumor Immune Dysfunction and Exclusion, chemosensitivity analysis between the high- and low-risk groups. The diagnostic ability of prognostic lncRNAs has also been validated. Finally, we validated the expression levels of selected prognostic lncRNAs by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS The prognostic model was constructed based on four prognostic lncRNAs (LINC00857, EP300-AS1, TBX5-AS1, SNHG3) related to lipid metabolism. The receiver operating characteristic curve (ROC) and Kaplan Meier (KM) curves of the risk model showed their validity. The results of Gene Set Enrichment Analysis suggested that differentially expressed genes in high- and low-risk groups were mainly enriched in immune response and cell cycle. There statistical differences in TMB and neoantigen between high- and low-risk groups. Drug sensitivity analysis suggested that patients with low risk scores may have better chemotherapy outcomes. The results of qRT-PCR were suggesting that compared with the normal group, the expressions of EP300-AS1 and TBX5-AS1 were down-regulated in the tumor group, while the expressions of LINC00857 and SNHG3 were up-regulated. The four prognostic lncRNAs had good diagnostic capabilities, and the overall diagnostic model of the four prognostic lncRNAs was more effective. CONCLUSION A total of 4 prognostic lncRNAs related to lipid metabolism were obtained and an effective risk model was constructed.
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Affiliation(s)
- Jie Zhao
- Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, China
| | - Guangjian Li
- Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, China
| | - Guangqiang Zhao
- Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, China
| | - Wei Wang
- Department of Thoracic Surgery, Taihe Hospital (Hubei University of Medicine), Shiyan, China
| | - Zhenghai Shen
- Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, China
| | - Yantao Yang
- Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, China
| | - Yunchao Huang
- Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, China
| | - Lianhua Ye
- Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, China
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Li N, Zeng A, Wang Q, Chen M, Zhu S, Song L. Regulatory function of DNA methylation mediated lncRNAs in gastric cancer. Cancer Cell Int 2022; 22:227. [PMID: 35810299 PMCID: PMC9270757 DOI: 10.1186/s12935-022-02648-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 06/28/2022] [Indexed: 12/31/2022] Open
Abstract
As one of the most common malignancies worldwide, gastric cancer contributes to cancer death with a high mortality rate partly responsible for its out-of-control progression as well as limited diagnosis. DNA methylation, one of the epigenetic events, plays an essential role in the carcinogenesis of many cancers, including gastric cancer. Long non-coding RNAs have emerged as the significant factors in the cancer progression functioned as the oncogene genes, the suppressor genes and regulators of signaling pathways over the decade. Intriguingly, increasing reports, recently, have claimed that abnormal DNA methylation regulates the expression of lncRNAs as tumor suppressor genes in gastric cancer and lncRNAs as regulators could exert the critical influence on tumor progression through acting on DNA methylation of other cancer-related genes. In this review, we summarized the DNA methylation-associated lncRNAs in gastric cancer which play a large impact on tumor progression, such as proliferation, invasion, metastasis and so on. Furthermore, the underlying molecular mechanism and signaling pathway might be developed as key points of gastric cancer range from diagnosis to prognosis and treatment in the future.
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Affiliation(s)
- Nan Li
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People's Republic of China
| | - Anqi Zeng
- Institute of Translational Pharmacology and Clinical Application, Sichuan Academy of Chinese Medical Science, Chengdu, Sichuan, 610041, People's Republic of China
| | - Qian Wang
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People's Republic of China
| | - Maohua Chen
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People's Republic of China
| | - Shaomi Zhu
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People's Republic of China.
| | - Linjiang Song
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People's Republic of China.
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Pan Q, Yi C, Zhang Y. Overall Survival Signature of 5-Methylcytosine Regulators Related Long Non-Coding RNA in Hepatocellular Carcinoma. Front Oncol 2022; 12:884377. [PMID: 35686101 PMCID: PMC9172585 DOI: 10.3389/fonc.2022.884377] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 04/08/2022] [Indexed: 12/28/2022] Open
Abstract
Purpose Studies reported that 5-methylcytosine (m5C) RNA transferase alters tumor progression; however, studies of m5C-related lncRNA remain lacking. This article intends to study the lncRNA modified by m5C RNA transferase in hepatocellular carcinoma using a combination of computational biology and basic experiments. Method We identified 13 m5C RNA transferase-related genes and selected long non-coding RNAs with a Pearson correlation coefficient greater than 0.4. Univariate Cox regression analysis was used to screen m5C RNA transferase lncRNA related to survival phenotype. We divided TCGA-LIHC into two types of m5C RNA using non-negative matrix decomposition. According to WGCNA, the co-expression models of two lncRNA regulation modes were constructed to analyze the characteristic biological processes of the two m5C RNA transferase-related lncRNA gene models. Then, a predictive model of m5C RNA transferase lncRNA was using LASSO regression. Finally, we used cell experiments, transwell experiments, and clone formation experiments to test the relationship between SNHG4 and tumor cell proliferation in Hep-G2 and Hep-3b cells line. Results We identified 436 m5C RNA transferase-related lncRNAs. Using univariate Cox regression analysis, 43 prognostic-related lncRNAs were determined according to P < 0.001. We divided TCGA-LIHC into two regulation modes of m5C RNA transferase using non-negative matrix factorization. The two regulation modes showed significant differences in overall and disease-free survival. We used LASSO to construct m5c-related lncRNA prognostic signature. Thus, a predictive m5C-lncRNA model was established using four lncRNAs: AC026412.3, AC010969.2, SNHG4, and AP003392.5. The score calculated by the m5C-lncRNA model significantly correlated with the overall survival of hepatocellular carcinoma. The receiver operating characteristic curve and decision curve analysis verified the accuracy of the predictive model. We observed a more robust immune response in the high-risk score group. The transwell experiments and clone formation experiments suggested that m5C RNA transferase-related lncRNA SNHG4 promotes the proliferation and migration of Hep-G2 and Hep-3b cells line. Conclusion Two lncRNA expression patterns regulated by m5C RNA transferase were identified. The difference between the two expression patterns and the survival phenotype in the biological process was pointed out. A 5-methylcytosine RNA methyltransferases-related lncRNA overall survival signature was constructed. These results provide some understanding of the influence of m5C transferase on hepatocellular carcinoma. The prediction model of m5C transferase lncRNA has potential clinical value in managing hepatocellular carcinoma.
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Affiliation(s)
- Qi Pan
- Key Laboratory of Organ Transplantation of Liaoning Province, Department of Hepatobiliary Surgery and Organ Transplantation, First Hospital of China Medical University, Shenyang, China
| | - Caiyu Yi
- China Medical University, Shenyang, China
| | - Yijie Zhang
- Key Laboratory of Organ Transplantation of Liaoning Province, Department of Hepatobiliary Surgery and Organ Transplantation, First Hospital of China Medical University, Shenyang, China
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Shan DD, Zheng QX, Wang J, Chen Z. Small nucleolar RNA host gene 3 functions as a novel biomarker in liver cancer and other tumour progression. World J Gastroenterol 2022; 28:1641-1655. [PMID: 35581965 PMCID: PMC9048787 DOI: 10.3748/wjg.v28.i16.1641] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/09/2022] [Accepted: 03/16/2022] [Indexed: 02/06/2023] Open
Abstract
Cancer has become the most life-threatening disease in the world. Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs, especially long noncoding RNAs (lncRNAs), have significant effects in human cancers. LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes. Small nucleolar RNA host gene 3 (SNHG3) is a novel lncRNA and has been reported to be differentially expressed in various tumors, such as liver cancer, gastric cancer, and glioma. However, the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood. In this review, we summarize the results of SNHG3 studies in humans, animal models, and cells to underline the expression and role of SNHG3 in cancer. SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis. SNHG3 expression in lung adenocarcinoma remains controversial. Concurrently, SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms, including competing endogenous RNA effects. A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.
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Affiliation(s)
- Dan-Dan Shan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Qiu-Xian Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Jing Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Zhi Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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Wang D, Zou L, Luo J, Zhang C, Feng H, Qin G. Potential diagnostic and prognostic value of the long non-coding RNA SNHG3 in human cancers: A systematic review and meta-analysis. Int J Biol Markers 2022; 37:3-12. [PMID: 35130083 DOI: 10.1177/03936155221077121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Small nucleolar RNA host gene 3 (SNHG3), as a novel long non-coding RNA (lncRNA) participates in the oncogenic processes of various cancers. We combined a systematic review and a meta-analysis to assess the potential role of SNHG3 as a pan-cancer marker for cancer diagnosis and prognosis. METHODS Our study comprehensively searched for SNHG3 expression profiling studies from PubMed, Web of Science, Excerpta Medica Database (EMBASE), Cochrane Library, Google Scholar, and The Cancer Genome Atlas (TCGA). The diagnostic capacity of SNHG3 for all cancers in TCGA database was evaluated from the perspective of pooled sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC) of the summary receiver operating characteristic (sROC) curve. Also, this research studied the correlation of SNHG3 expression and the overall survival to access its prognostic value. RESULTS A sum total of 11,888 cancer patients and 730 controls from 44 eligible studies were enrolled in this integrated analysis. In TCGA database, SNHG3 was significantly upregulated in most types of cancers (16/33, 48%). The pooled sensitivity, specificity, and DOR with 95% CIs was 0.72 (95% CI: 0.60-0.82), 0.87 (95% CI: 0.84-0.90), and 18 (95% CI: 11-30), respectively. Similarly, the AUC of the sROC curve was 0.89 (95% CI: 0.86-0.92), indicating SNHG3 was highly conserved as a diagnosis biomarker. Additionally, SNHG3 overexpression significantly deteriorated the overall survival of cancer patients (pooled HR = 1.28, 95% CI:1.11-1.48; P < 0.05). CONCLUSIONS These findings suggest that the lncRNA SNHG3 could serve as a promising diagnostic and prognostic biomarker.
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Affiliation(s)
- Dingting Wang
- Department of Otolaryngology Head and Neck Surgery, 556508Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Longfei Zou
- Department of Orthopedic Surgery, 556508Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jian Luo
- Department of Otolaryngology Head and Neck Surgery, The First People's Hospital of Yibin, Yibin, China
| | - Conghong Zhang
- Department of Otolaryngology Head and Neck Surgery, Sichuan Province Panzhihua Central Hospital, Panzhihua, China * These authors contributed equally to this work
| | - Huajun Feng
- Department of Otolaryngology Head and Neck Surgery, 556508Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Gang Qin
- Department of Otolaryngology Head and Neck Surgery, 556508Affiliated Hospital of Southwest Medical University, Luzhou, China
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A diagnostic and prognostic value of blood-based circulating long non-coding RNAs in Thyroid, Pancreatic and Ovarian Cancer. Crit Rev Oncol Hematol 2022; 171:103598. [PMID: 35033662 DOI: 10.1016/j.critrevonc.2022.103598] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 01/12/2022] [Accepted: 01/12/2022] [Indexed: 12/12/2022] Open
Abstract
Several studies have demonstrated the potential of circulating long non-coding RNAs (lncRNAs) as promising cancer biomarkers. Herein, we addressed the regulatory role of circulating lncRNAs and their potential value as diagnostic/prognostic markers for thyroid, pancreatic and ovarian cancers. Furthermore, we analyzed and measured the clinical implications and association of lncRNAs with sensitivity, specificity, and area under the ROC curve (AUC). Based on our meta-analysis, we found that GAS8-AS1 could discriminate thyroid cancer from non-cancer and other cancers with higher accuracy (AUC = 0.746; sensitivity = 61.70%, and specificity = 90.00%). Similarly, for ovarian cancer, lncRNA RP5-837J1.2 was found to have ideal diagnostic potential with critical clinical specifications of AUC = 0.996; sensitivity = 97.30% and specificity = 94.60%. Whereas we could not find any lncRNA having high diagnostic/prognostic efficiency in pancreatic cancer. We believe that lncRNAs mentioned above may explore clinical settings for the diagnosis and prognosis of cancer patients.
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Xu Z, Ye J, Bao P, Wu Q, Xie F, Li P. Long non-coding RNA SNHG3 promotes the progression of clear cell renal cell carcinoma via regulating BIRC5 expression. Transl Cancer Res 2021; 10:4502-4513. [PMID: 35116306 PMCID: PMC8798718 DOI: 10.21037/tcr-21-1802] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 09/29/2021] [Indexed: 01/02/2023]
Abstract
Background Research has shown that the progression of clear cell renal cell carcinoma (ccRCC) is modulated by long non-coding RNAs (lncRNAs). However, the roles of specific lncRNAs in the malignancy of ccRCC are still unknown. Methods TCGA and GSE66272 datasets were used to predict differentially expressed genes (DEGs) in ccRCC. ENCORI database was employed to display BIRC5 miRNA network and potential lncRNA interactions for miRNAs. KM plotter and correlation analyses were performed to identify the overall survival (OS)- and BIRC5-related miRNAs. Quantitative real-time PCR (qRT-PCR) was used to verify the BIRC5 mRNA in the seventy paired clinical samples of ccRCC tissues. The ccRCC A498 and 786-O were individually transfected with lncRNA SNHG3 and LINC00997 and then western blotting was used to detect the BIRC5 protein expression. The Dual-luciferase reporter assay was used to examine the regulatory interaction between lncRNA SNHG3 and microRNA (miRNA/miR)-10b-5p. Results BICR5 is associated with the progression of ccRCC. The two novel lncRNAs (LINC00997, SNHG3) were up-regulated in ccRCC tissues and positively with the BICR5 protein expression. However, Suppressing SNHG3 expression reduced BIRC5 protein expression compared with the LINC00997, most importantly, Suppressing SNHG3 expression suppressed tumor progression in vitro. In addition, SNHG3 promotes the expression of BIRC5 protein by sponging microRNA-10b-5p. Conclusions Our findings suggest that SNHG3 plays a vital role in promoting ccRCC via the microRNA-10b-5p/BIRC5 axis and may serve as a novel therapeutic target for the treatment of patients with ccRCC.
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Affiliation(s)
- Zhaoyu Xu
- Department of Urology, Lishui People's Hospital, Lishui, China
| | - Junjie Ye
- Department of Urology, Lishui People's Hospital, Lishui, China
| | - Pengfei Bao
- Department of Urology, Lishui People's Hospital, Lishui, China
| | - Qi Wu
- Department of Urology, Lishui People's Hospital, Lishui, China
| | - Fuchen Xie
- Department of Urology, Lishui People's Hospital, Lishui, China
| | - Peng Li
- Department of Urology, Lishui People's Hospital, Lishui, China
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Tian X, Shen L, Wang Z, Zhou L, Peng L. A novel lncRNA-protein interaction prediction method based on deep forest with cascade forest structure. Sci Rep 2021; 11:18881. [PMID: 34556758 PMCID: PMC8460650 DOI: 10.1038/s41598-021-98277-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 08/18/2021] [Indexed: 02/08/2023] Open
Abstract
Long noncoding RNAs (lncRNAs) regulate many biological processes by interacting with corresponding RNA-binding proteins. The identification of lncRNA-protein Interactions (LPIs) is significantly important to well characterize the biological functions and mechanisms of lncRNAs. Existing computational methods have been effectively applied to LPI prediction. However, the majority of them were evaluated only on one LPI dataset, thereby resulting in prediction bias. More importantly, part of models did not discover possible LPIs for new lncRNAs (or proteins). In addition, the prediction performance remains limited. To solve with the above problems, in this study, we develop a Deep Forest-based LPI prediction method (LPIDF). First, five LPI datasets are obtained and the corresponding sequence information of lncRNAs and proteins are collected. Second, features of lncRNAs and proteins are constructed based on four-nucleotide composition and BioSeq2vec with encoder-decoder structure, respectively. Finally, a deep forest model with cascade forest structure is developed to find new LPIs. We compare LPIDF with four classical association prediction models based on three fivefold cross validations on lncRNAs, proteins, and LPIs. LPIDF obtains better average AUCs of 0.9012, 0.6937 and 0.9457, and the best average AUPRs of 0.9022, 0.6860, and 0.9382, respectively, for the three CVs, significantly outperforming other methods. The results show that the lncRNA FTX may interact with the protein P35637 and needs further validation.
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Affiliation(s)
- Xiongfei Tian
- School of Computer Science, Hunan University of Technology, Zhuzhou, 412007, China
| | - Ling Shen
- School of Computer Science, Hunan University of Technology, Zhuzhou, 412007, China
| | - Zhenwu Wang
- School of Computer Science, Hunan University of Technology, Zhuzhou, 412007, China
| | - Liqian Zhou
- School of Computer Science, Hunan University of Technology, Zhuzhou, 412007, China.
| | - Lihong Peng
- School of Computer Science, Hunan University of Technology, Zhuzhou, 412007, China.
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Rao J, Fu J, Meng C, Huang J, Qin X, Zhuang S. LncRNA SNHG3 Promotes Gastric Cancer Cells Proliferation, Migration, and Invasion by Targeting miR-326. JOURNAL OF ONCOLOGY 2021; 2021:9935410. [PMID: 34257656 PMCID: PMC8260314 DOI: 10.1155/2021/9935410] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 06/16/2021] [Indexed: 12/18/2022]
Abstract
The function and possible mechanism of lncRNA Small Nucleolar RNA Host Gene 3 (SNHG3) in GC have not been fully studied. The aim of our study was to investigate the role of SNHG3 in the proliferation, migration, and invasion of GC cell lines. The expressions of SNHG3, miR-326, and TWIST in GC9811-P GC cell lines were detected by RT-qPCR. Western blotting was performed to detect the protein levels of TWIST and EMT-related genes. Luciferase reporter gene analysis and RNA immunoprecipitation (RIP) analysis confirmed the interaction between lncRNA SNHG3, miR-326, and TWIST. CCK-8 and Transwell assays were performed to detect cell proliferation, invasion, and migration abilities. The results showed that lncRNA SNHG3 and TWIST were highly expressed in GC cell lines, while miR-326 was expressed to a low degree. Moreover, lncRNA SNHG3 knockdown or miR-326 overexpression significantly inhibited cell proliferation, migration, and invasion of GC cell lines. In addition, TWIST overexpression can reverse the inhibition of lncRNA SNHG3 knockdown or miR-326 overexpression on cell proliferation, migration, and invasion. In conclusion, lncRNA SNHG3 may promote GC progression through the miR-326/TWIST axis, which may provide a new diagnostic and prognostic biomarker for GC.
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Affiliation(s)
- Jun Rao
- Department of Gastroenterology, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, No. 29 Xinglong District, Changzhou 213000, China
| | - Jinjin Fu
- Department of Gastroenterology, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, No. 29 Xinglong District, Changzhou 213000, China
| | - Chuchen Meng
- Department of Endocrinology, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, China
| | - Jin Huang
- Department of Gastroenterology, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, No. 29 Xinglong District, Changzhou 213000, China
| | - Xiangrong Qin
- Department of Gastroenterology, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, No. 29 Xinglong District, Changzhou 213000, China
| | - Shaohua Zhuang
- Department of Gastroenterology, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, No. 29 Xinglong District, Changzhou 213000, China
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12
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Zamaraev AV, Volik PI, Sukhikh GT, Kopeina GS, Zhivotovsky B. Long non-coding RNAs: A view to kill ovarian cancer. Biochim Biophys Acta Rev Cancer 2021; 1876:188584. [PMID: 34157315 DOI: 10.1016/j.bbcan.2021.188584] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/15/2021] [Accepted: 06/16/2021] [Indexed: 12/22/2022]
Abstract
An emerging role of long non-coding RNAs (lncRNAs) in tumor progression has been revealed in the last decade. Through interactions with nucleic acids and proteins, lncRNAs could act as enhancers, scaffolds or decoys for a number of oncoproteins and tumor suppressors. The aberrant lncRNA expression or mutations are often associated with changes in a variety of cellular processes, including proliferation, stress response and cell death. Here, we will focus on the tumor-associated lncRNAs in ovarian cancer according to their contribution to cancer hallmarks, such as intense proliferation, cell death resistance, altered energy metabolism, invasion and metastasis, and immune evasion. Moreover, the potential clinical implications of lncRNAs and their significance for the diagnosis, prognosis and therapy of ovarian cancer will be discussed.
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Affiliation(s)
- Alexey V Zamaraev
- Faculty of Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia
| | - Pavel I Volik
- Faculty of Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia
| | - Gennady T Sukhikh
- V. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia
| | - Gelina S Kopeina
- Faculty of Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia.
| | - Boris Zhivotovsky
- Faculty of Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia; Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.
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Overexpression of lncRNA SNGH3 Predicts Unfavorable Prognosis and Clinical Outcomes in Human Cancers: Evidence from a Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2021; 2020:7974034. [PMID: 32802874 PMCID: PMC7335396 DOI: 10.1155/2020/7974034] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 05/23/2020] [Accepted: 05/28/2020] [Indexed: 12/22/2022]
Abstract
Long noncoding RNAs (lncRNAs) have been confirmed to play a crucial role in human disease, especially in tumor development and progression. Small nucleolar RNA host gene (SNHG3), a newly identified lncRNA, has been found dysregulated in various cancers. Nevertheless, the results remain controversial. Thus, we aim to analyze the comprehensive data to elaborate the association between SNHG3 expression and clinical outcomes in multiple cancers. We searched PubMed, Web of Science, Cochrane Library, Embase, and MEDLINE database to identify eligible articles. STATA software was applied to calculate the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (95% CI) for survival outcomes and clinical parameters, respectively. Besides, the data from The Cancer Genome Atlas (TCGA) dataset was extracted to verify the results in our meta-analysis. There were thirteen studies totaling 919 cancer patients involved in this meta-analysis. The results demonstrated that high SNHG3 expression was significantly associated with poor overall survival (OS) (HR = 2.53, 95% CI: 1.94-3.31) in cancers, disease-free survival (DFS) (HR = 3.89, 95% CI: 1.34-11.3), and recurrence-free survival (RFS) (HR = 2.42, 95% CI: 1.14-5.15) in hepatocellular carcinoma. Analysis stratified by analysis method, sample size, follow-up time, and cancer type further verified the prognostic value of SNHG3. Additionally, patients with high SNHG3 expression tended to have more advanced clinical stage, higher histological grade, earlier distant metastasis, and earlier lymph node metastasis. Excavation of TCGA dataset valuated that SNHG3 was upregulated in various cancers and predicted worse OS and DFS. Overexpressed SNHG3 was strongly associated with poor survival and clinical outcomes in human cancers and therefore can serve as a promising biomarker for predicting patients' prognosis.
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Non-Coding RNAs as Biomarkers of Tumor Progression and Metastatic Spread in Epithelial Ovarian Cancer. Cancers (Basel) 2021; 13:cancers13081839. [PMID: 33921525 PMCID: PMC8069230 DOI: 10.3390/cancers13081839] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/08/2021] [Accepted: 04/08/2021] [Indexed: 12/20/2022] Open
Abstract
Simple Summary Despite advances in cancer research in recent years, efficient predictive biomarkers of tumor progression and metastatic spread for ovarian cancer are still missing. Therefore, we critically address recent findings in the field of non-coding RNAs (microRNAs and long non-coding RNAs) and DNA methylation in ovarian cancer patients as promising novel biomarkers of ovarian cancer progression. Abstract Ovarian cancer is one of the most common causes of death among gynecological malignancies. Molecular changes occurring in the primary tumor lead to metastatic spread into the peritoneum and the formation of distant metastases. Identification of these changes helps to reveal the nature of metastases development and decipher early biomarkers of prognosis and disease progression. Comparing differences in gene expression profiles between primary tumors and metastases, together with disclosing their epigenetic regulation, provides interesting associations with progression and metastasizing. Regulatory elements from the non-coding RNA families such as microRNAs and long non-coding RNAs seem to participate in these processes and represent potential molecular biomarkers of patient prognosis. Progress in therapy individualization and its proper targeting also rely upon a better understanding of interactions among the above-listed factors. This review aims to summarize currently available findings of microRNAs and long non-coding RNAs linked with tumor progression and metastatic process in ovarian cancer. These biomolecules provide promising tools for monitoring the patient’s response to treatment, and further they serve as potential therapeutic targets of this deadly disease.
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15
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Zhang L, Li G, Wang X, Zhang Y, Huang X, Wu H. lncRNA SNHG3 acts as oncogene in ovarian cancer through miR-139-5p and Notch1. Oncol Lett 2021; 21:122. [PMID: 33552243 PMCID: PMC7798025 DOI: 10.3892/ol.2020.12383] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 10/09/2020] [Indexed: 12/15/2022] Open
Abstract
Ovarian cancer (OC) is a common malignant tumor of the female reproductive system. Long non-coding RNAs (lncRNAs) play an important role in OC occurrence and development. Thus, the function and potential mechanism of lncRNA small nucleolar RNA host gene 3 (SNHG3) was explored in the development of OC. The expression of SNHG3, microRNA (miR)-139-5p and Notch homolog 1, translocation-associated (Drosophila) (Notch1) in OC were detected by RT-qPCR or western blot assay. In addition, CCK-8 and wound-healing assays were used to detect OVCAR3 proliferation and migration ability. The targeting relationship of miR-139-5p with SNHG3 or Notch1 was verified through luciferase reporter assay. Rescue experiments were performed to confirm whether SNHG3 could mediate OVCAR3 proliferation and migration through miR-139-5p and Notch1. In OC tissues and cell lines, the expression of SNHG3 and Notch1 were significantly increased, and the expression of miR-139-5p was significantly decreased. SNHG3 inhibition suppressed the proliferation and migration of OVCAR3 cells. Luciferase reporter experiment confirmed that miR-139-5p could target SNHG3 and Notch1. Transfection of miR-139-5p inhibitor significantly reversed the inhibitory effect of SNHG3 knockdown on OVCAR3 proliferation and migration. Moreover, SNHG3 inhibition or miR-139-5p mimic abolished the promotion of Notch1 overexpression on OVCAR3 proliferation and migration. In conclusion, SNHG3 could accelerate the proliferation and migration of OC cells by regulating miR-139-5p and Notch1.
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Affiliation(s)
- Li Zhang
- The Obstetric Ward, Jinan Maternal and Child Health Care Hospital, Jinan, Shandong 250001, P.R. China
| | - Guihua Li
- Department of Clinical Laboratory, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China
| | - Xiuzhen Wang
- Department of Clinical Nutrition, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China
| | - Youli Zhang
- Department of Cardiology, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China
| | - Xia Huang
- Infectious Department, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China
| | - Huazhen Wu
- Department of Gynaecology, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China
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16
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Li Y, Gao L, Zhang C, Meng J. LncRNA SNHG3 Promotes Proliferation and Metastasis of Non-Small-Cell Lung Cancer Cells Through miR-515-5p/SUMO2 Axis. Technol Cancer Res Treat 2021; 20:15330338211019376. [PMID: 34032148 PMCID: PMC8155750 DOI: 10.1177/15330338211019376] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 04/23/2021] [Accepted: 05/03/2021] [Indexed: 12/13/2022] Open
Abstract
Lung cancer is a global disease and a major cause of cancer-related mortality worldwide. Accumulated studies have confirmed the essential role of long non-coding RNAs (lncRNAs) in the occurrence and development of cancers. Meanwhile, there have been reports concerning the role of Small Nucleolar RNA Host Gene 3 (SNHG3) in various cancers. However, there are so far few studies on the function and mechanism of SNHG3 in lung cancer. In the present study, SNHG3 was found to be highly expressed in lung cancer tissues and cells. Downregulation of SNHG3 could inhibit cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process. In addition, SNHG3 was found to have the ability to bind to miR-515-5p. Furthermore, Small Ubiquitin Like Modifier 2 (SUMO2) was identified to be the downstream target of miR-515-5p, which was negatively correlated with miR-515-5p expression. SNHG3 could positively regulate SUMO2 expression by sponging miR-515-5p. In addition, the rescue experiment showed that simultaneous transfection of miR-515-5p or SUMO2 siRNA could reverse the effect of SNHG3 expression on cell proliferation and metastasis. Collectively, our study demonstrates that SNHG3 can act on miR-515-5p in the form of competitive endogenous RNA (ceRNA) to regulate SUMO2 positively and thus affect the proliferation and metastasis of NSCLC cells. Findings in our study support that SNHG3/miR-515-5p/SUMO2 regulatory axis may become a potential therapeutic target for lung cancer.
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Affiliation(s)
- Yongqun Li
- Department of Respiratory Medicine, The Sixth Medical Center of PLA
General Hospital, Beijing, China
| | - Lipin Gao
- Department of Hematology, The Sixth Medical Center of PLA General
Hospital, Beijing, China
| | - Caiyun Zhang
- Department of Respiratory Medicine, The Sixth Medical Center of PLA
General Hospital, Beijing, China
| | - Jiguang Meng
- Department of Respiratory Medicine, The Sixth Medical Center of PLA
General Hospital, Beijing, China
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Xu B, Mei J, Ji W, Bian Z, Jiao J, Sun J, Shao J. LncRNA SNHG3, a potential oncogene in human cancers. Cancer Cell Int 2020; 20:536. [PMID: 33292213 PMCID: PMC7640707 DOI: 10.1186/s12935-020-01608-x] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 10/15/2020] [Indexed: 02/06/2023] Open
Abstract
Long noncoding RNAs (lncRNAs) are composed of > 200 nucleotides; they lack the ability to encode proteins but play important roles in a variety of human tumors. A large number of studies have shown that dysregulated expression of lncRNAs is related to tumor oncogenesis and progression. Emerging evidence shows that SNHG3 is a novel oncogenic lncRNA that is abnormally expressed in various tumors, including osteosarcoma, liver cancer, lung cancer, etc. SNHG3 primarily competes as a competitive endogenous RNA (ceRNA) that targets tumor suppressor microRNAs (miRNAs) and ceRNA mechanisms that regulate biological processes of tumors. In addition, abnormal expression of SNHG3 is significantly correlated with patient clinical features. Upregulation of SNHG3 contributes to biological functions, including tumor cell proliferation, migration, invasion and EMT. Therefore, SNHG3 may represent a potential diagnostic and prognostic biomarker, as well as a novel therapeutic target.
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Affiliation(s)
- Bin Xu
- Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qing Yang Road, Wuxi, 214023, Jiangsu, China
| | - Jie Mei
- Department of Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, P. R. China
| | - Wei Ji
- Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qing Yang Road, Wuxi, 214023, Jiangsu, China
| | - Zheng Bian
- Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qing Yang Road, Wuxi, 214023, Jiangsu, China
| | - Jiantong Jiao
- Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qing Yang Road, Wuxi, 214023, Jiangsu, China
| | - Jun Sun
- Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qing Yang Road, Wuxi, 214023, Jiangsu, China.
| | - Junfei Shao
- Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qing Yang Road, Wuxi, 214023, Jiangsu, China.
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18
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Sun B, Han Y, Cai H, Huang H, Xuan Y. Long non-coding RNA SNHG3, induced by IL-6/STAT3 transactivation, promotes stem cell-like properties of gastric cancer cells by regulating the miR-3619-5p/ARL2 axis. Cell Oncol (Dordr) 2020; 44:179-192. [PMID: 32930970 DOI: 10.1007/s13402-020-00560-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 08/31/2020] [Accepted: 09/04/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Chemotherapy is, next to surgery and radiotherapy, the mainstay regimen for the clinical management of gastric cancer. This therapy is, however, heavily compromised by the acquisition of resistance. Here, we aimed to clarify the potential involvement of long non-coding RNA SNGH3 in the acquisition of cisplatin resistance and stemness in gastric cancer. METHODS Cell viability and proliferation were measured using Cell Counting Kit-8 and colony formation assays, respectively. Stem cell-like cell growth was evaluated using a mammosphere formation assay. RNA levels of SNHG2, OCT-4, SOX-2, CD44, miR-3619-5p and ARL2 were determined using qRT-PCR, whereas protein levels of OCT-4, SOX-2, CD44, ARL2, STAT3 and pSTAT3 were determined using Western blotting. Dual luciferase reporter assays were employed to interrogate regulatory interactions between STAT3, SNHG3, miR-3619-5p and ARL2, respectively. Direct binding of STAT3 to the SNHG3 promoter was investigated using a chromatin immunoprecipitation assay. RESULTS We found that IL-6 triggered stem cell-like properties in cisplatin-treated gastric cancer cells and activated STAT3, which in turn transcriptionally regulated SNHG3 expression. SNHG3 expression up-regulation positively correlated with cisplatin resistance and stemness of gastric cancer cells, while SNHG3 down-regulation inhibited stem cell-like properties. In addition, we found that SNHG3 up-regulated ARL2 expression through sponging miR-3619-5p, which predominantly mediated the oncogenic properties of SNHG3 in this disease. CONCLUSIONS Our data indicate an involvement of aberrant SNHG3 over-expression in the acquisition of both cisplatin resistance and stemness of gastric cancer cells, and of the IL-6/STAT3/SNHG3/miR-3619-5p/ARL2 signaling cascade in the oncogenic properties of SNHG3.
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Affiliation(s)
- Bo Sun
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, No. 270 Dongan Road, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
| | - Yang Han
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, No. 270 Dongan Road, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
| | - Hong Cai
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, No. 270 Dongan Road, 200032, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China.
| | - Hua Huang
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, No. 270 Dongan Road, 200032, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China.
| | - Yi Xuan
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, No. 270 Dongan Road, 200032, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China.
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Zhang X, Zheng W, Jiang W, Lin R, Xing C. Long non-coding RNA SNHG3 accelerates progression in glioma by modulating miR-384/HDGF axis. Open Life Sci 2020; 15:654-664. [PMID: 33817254 PMCID: PMC7747505 DOI: 10.1515/biol-2020-0066] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 05/21/2020] [Accepted: 05/21/2020] [Indexed: 12/14/2022] Open
Abstract
Glioma is a malignant primary brain tumor that occurs in the central nervous system and has threatened the well-being of millions of patients. It is well acknowledged that long non-coding RNA (lncRNA) SNHG3 participates in the regulation of proliferation, inflation, differentiation, and metastasis in many cancers. However, the regulatory effect of SNHG3 on glioma progression is still controversial. The expression of SNHG3 and HDGF was upregulated, whereas miR-384 was downregulated in glioma tissues, compared with the normal tissues. Interestingly, high SNHG3 contributed to low survival rate while low SNHG3 showed the opposite result. Moreover, SNHG3 or HDGF knockdown significantly suppressed proliferation, migration, and invasion and induced apoptosis in glioma. Meanwhile, restoration of HDGF abrogated the inhibition of SNHG3 silencing on glioma cell progression. Besides, miR-384 inhibitor attenuated SNHG3 silencing induced inhibition on HDGF mRNA and protein expression in A172 and SHG44 cells. LncRNA SNHG3 promotes cell proliferation, migration, and invasion in glioma by enhancing HDGF expression via miR-384 sponging, representing the promising targets for the development of novel therapeutic strategies.
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Affiliation(s)
- Xiaofeng Zhang
- Department of Neurosurgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China
| | - Weixin Zheng
- Department of Neurosurgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China
| | - Wenting Jiang
- Department of Ultrasound, Zhangzhou Affiliated Hospital of Fujian Medical University, No. 59 Shengli Road, Zhangzhou, Fujian, China
| | - Ruisheng Lin
- Department of Neurosurgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China
| | - Chunyang Xing
- Department of Neurosurgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China
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20
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Jiang H, Li X, Wang W, Dong H. Long non-coding RNA SNHG3 promotes breast cancer cell proliferation and metastasis by binding to microRNA-154-3p and activating the notch signaling pathway. BMC Cancer 2020; 20:838. [PMID: 32883233 PMCID: PMC7469338 DOI: 10.1186/s12885-020-07275-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 08/09/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Breast cancer (BC) is a malignant tumor that occurs in the epithelial tissue of the breast gland. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) has been found to promote BC cell proliferation and invasion by regulating the microRNA (miR)-101/zinc-finger enhancer binding axis in BC. Herein, the objective of the present study is to evaluate the effect of lncRNA SNHG3 on BC cell proliferation and metastasis with the Notch signaling pathway. METHODS Differentially expressed lncRNA in BC tissues and normal breast tissues was analyzed. SNHG3 si-RNA-1 and SNHG3 si-RNA-2 were constructed to detect the mechanism of SNHG3 interference in BC cell proliferation, viability, migration and invasion. Then, dual-luciferase reporter gene assay was utilized to verify the binding relation between SNHG3 and miR-154-3p as well as miR-154-3p and Notch2. Moreover, xenograft transplantation was applied to confirm the in vitro experiments. RESULTS Highly expressed SNHG3 was observed in BC tissues. The growth of BC cells in vivo and in vitro was evidently repressed after silencing SNHG3. BC cell invasion and migration were inhibited by silencing SNHG3 in vitro. SNHG3 could act as a competing endogenous RNA of miR-154-3p and upregulate the Notch signaling pathway to promote BC cell development. Activation of the Notch signaling pathway can partly reverse the inhibition of cell activity induced by silencing SNHG3. CONCLUSION Our study demonstrated that interfered lncRNA SNHG3 promoted BC cell proliferation and metastasis by activating the Notch signaling pathway. This investigation may offer new insight for BC treatment.
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Affiliation(s)
- Hongnan Jiang
- Department of Breast Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China
| | - Xiaojun Li
- Department of Rdaiology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China
| | - Wei Wang
- Department of Breast Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China
| | - Honglin Dong
- Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan, 030001, Shanxi, PR China.
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Qin Y, Sun W, Wang Z, Dong W, He L, Zhang T, Zhang H. Long Non-Coding Small Nucleolar RNA Host Genes (SNHGs) in Endocrine-Related Cancers. Onco Targets Ther 2020; 13:7699-7717. [PMID: 32848414 PMCID: PMC7417930 DOI: 10.2147/ott.s267140] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 07/17/2020] [Indexed: 12/24/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) are emerging regulators of a diverse range of biological processes through various mechanisms. Genome-wide association studies of tumor samples have identified several lncRNAs, which act as either oncogenes or tumor suppressors in various types of cancers. Small nucleolar RNAs (snoRNAs) are predominantly found in the nucleolus and function as guide RNAs for the processing of transcription. As the host genes of snoRNAs, lncRNA small nucleolar RNA host genes (SNHGs) have been shown to be abnormally expressed in multiple cancers and can participate in cell proliferation, tumor progression, metastasis, and chemoresistance. Here, we review the biological functions and emerging mechanisms of SNHGs involved in the development and progression of endocrine-related cancers including thyroid cancer, breast cancer, pancreatic cancer, ovarian cancer and prostate cancer.
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Affiliation(s)
- Yuan Qin
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, People's Republic of China
| | - Wei Sun
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, People's Republic of China
| | - Zhihong Wang
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, People's Republic of China
| | - Wenwu Dong
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, People's Republic of China
| | - Liang He
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, People's Republic of China
| | - Ting Zhang
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, People's Republic of China
| | - Hao Zhang
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, People's Republic of China
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Zhang H, Wei N, Zhang W, Shen L, Ding R, Li Q, Li S, Du Y. lncRNA SNHG3 promotes breast cancer progression by acting as a miR‑326 sponge. Oncol Rep 2020; 44:1502-1510. [PMID: 32945476 PMCID: PMC7448486 DOI: 10.3892/or.2020.7690] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Accepted: 05/15/2020] [Indexed: 12/14/2022] Open
Abstract
Accumulating evidence suggests that long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SHNG3) plays crucial roles in the initiation and progression of various types of malignant cancers. Yet, the role played by SNHG3 in breast cancer as well as the associated mechanisms remain largely unclear. The expression of SNHG3 was detected in breast cancer tissues and cell lines by reverse-transcription quantitative PCR (RT-qPCR). Cell proliferation, colony formation, cell cycle distribution, migration and invasion abilities were detected by Cell Counting Kit-8, colony formation assay, flow cytometry, wound-healing and Matrigel invasion assays, respectively. The regulatory relationships between SNHG3 and miR-326 were explored by luciferase reporter assay. A nude mouse model was established to investigate the effect of SNHG3 in vivo. The results showed an upregulation of SNHG3 in breast cancer tissues and cell lines. Loss-of-function assays revealed significant suppression of breast cancer behaviors such as: Abilities to proliferate, form colonies, migrate and invade in vitro coupled with a delayed growth of tumors in vivo when SNHG3 was knocked down. Mechanically, it was shown that SNHG3 served as a competing endogenous RNA (ceRNA) of miR-326 that in turn is a tumor suppressor in this cancer. The correlation between the expression of SNHG3 and miR-326 was found to be strongly negative in these samples. Additionally, we found that inhibition of SNHG3 caused a partially reversal in the inhibition exerted by miR-326 on the ability of these cells to proliferate, form colonies, migrate and invade. Collectively, these findings suggest the functioning of SNHG3 as a ceRNA to enhance the ability of breast cancer cells to proliferate and metastasize to putatively serve as a new target to explore therapeutic intervention of this malignancy.
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Affiliation(s)
- Haipeng Zhang
- Department of Gynecology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Na Wei
- Department of First Operating Room, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Wei Zhang
- Department of Cosmetology Plastic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Lishennan Shen
- Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Rongbo Ding
- Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Qian Li
- Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Simin Li
- Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Ye Du
- Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
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Li Y, Zhao Z, Liu W, Li X. SNHG3 Functions as miRNA Sponge to Promote Breast Cancer Cells Growth Through the Metabolic Reprogramming. Appl Biochem Biotechnol 2020; 191:1084-1099. [PMID: 31956955 PMCID: PMC7320061 DOI: 10.1007/s12010-020-03244-7] [Citation(s) in RCA: 95] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Accepted: 01/08/2020] [Indexed: 12/11/2022]
Abstract
Cancer-associated fibroblasts (CAFs) are important ingredient in tumor microenvironment. The dynamic interplay between CAFs and cancer cells plays essential roles during tumor development and progression. However, the mechanisms of intercellular communication between CAFs and cancer cells remain largely unknown. We characterized exosomes secreted from breast cancer patient-derived CAFs by transmission electron microscopy. The expression of SNHG3, miR-330-5p, and PKM (Pyruvate Kinase M1/M2) was examined by real-time QPCR and immunoblot. The function of SNHG3 on the growth and metabolism of tumor cells was used by CCK8 and mitochondrial oxygen consumption assays. The binding between SNHG3, miR-330-5p, and PKM was examined by dual luciferase reporter assays. Orthotopical xenograft of breast tumor experiments was performed to determine the function of SNHG3 in vivo. We demonstrated that exosomes secreted from CAFs reprogram the metabolic pathways after tumor cells uptake the exosomes. CAF-secreted exosomal lncRNA SNHG3 served as a molecular sponge for miR-330-5p in breast cancer cells. Moreover, PKM could be targeted by miR-330-5p and was controlled by SNHG3 in breast cancer cells. Mechanistically, SNHG3 knockdown in CAF-secreted exosomes suppressed glycolysis metabolism and cell proliferation by the increase of miR-330-5p and decrease of PKM expression in tumor cells. SNHG3 functions as a miR-330-5p sponge to positively regulate PKM expression, inhibit mitochondrial oxidative phosphorylation, increase glycolysis carboxylation, and enhance breast tumor cell proliferation. Overall, SNHG3 could play a major role in the development and progression of breast cancer and support the therapeutic potential of targeting communication between cancer cells and tumor microenvironment.
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Affiliation(s)
- Yan Li
- Breast Internal Medicine Department, The 3rd Affiliated Teaching Hospital of XinJiang Medical University (Affiliated Cancer Hospital), Urumqi, 830011 China
| | - Zhenhui Zhao
- Breast Internal Medicine Department, The 3rd Affiliated Teaching Hospital of XinJiang Medical University (Affiliated Cancer Hospital), Urumqi, 830011 China
| | - Wei Liu
- Breast Internal Medicine Department, The 3rd Affiliated Teaching Hospital of XinJiang Medical University (Affiliated Cancer Hospital), Urumqi, 830011 China
| | - Xun Li
- Breast Internal Medicine Department, The 3rd Affiliated Teaching Hospital of XinJiang Medical University (Affiliated Cancer Hospital), Urumqi, 830011 China
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24
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Li N, Zhan X. Anti-parasite drug ivermectin can suppress ovarian cancer by regulating lncRNA-EIF4A3-mRNA axes. EPMA J 2020; 11:289-309. [PMID: 32549918 PMCID: PMC7272521 DOI: 10.1007/s13167-020-00209-y] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 05/07/2020] [Indexed: 12/16/2022]
Abstract
RELEVANCE Ivermectin, as an old anti-parasite drug, can suppress almost completely the growth of various human cancers, including ovarian cancer (OC). However, its anticancer mechanism remained to be further studied at the molecular levels. Ivermectin-related molecule-panel changes will serve a useful tool for its personalized drug therapy and prognostic assessment in OCs. PURPOSE To explore the functional significance of ivermectin-mediated lncRNA-EIF4A3-mRNA axes in OCs and ivermectin-related molecule-panel for its personalized drug therapy monitoring. METHODS Based on our previous study, a total of 16 lncRNA expression patterns were analyzed using qRT-PCR before and after ivermectin-treated different OC cell lines (TOV-21G and A2780). Stable isotope labeling with amino acids in cell culture (SILAC)-based quantitative proteomics was used to analyze the protein expressions of EIF4A3 and EIF4A3-binding mRNAs in ovarian cancer cells treated with and without ivermectin. A total of 411 OC patients from the Cancer Genome Atlas (TCGA) database with the selected lncRNA expressions and the corresponding clinical data were included. Lasso regression was constructed to examine the relationship between lncRNA signature and OC survival risk. The overall survival analysis between high-risk and low-risk groups used the Kaplan-Meier method. Heatmap showed the correlation between risk groups and clinical characteristics. The univariate and multivariate models were established with Cox regression. RESULTS SILAC-based quantitative proteomics found the protein expression levels of EIF4A3 and 116 EIF4A3-binding mRNAs were inhibited by ivermectin in OC cells. Among the analyzed 16 lncRNAs (HCG15, KIF9-AS1, PDCD4-AS1, ZNF674-AS1, ZNRF3-AS1, SOS1-IT1, LINC00565, SNHG3, PLCH1-AS1, WWTR1-AS1, LINC00517, AL109767.1, STARD13-IT1, LBX2-AS1, LEMD1-AS1, and HOXC-AS3), only 7 lncRNAs (HCG15, KIF9-AS1, PDCD4-AS1, ZNF674-AS1, ZNRF3-AS1, SOS1-IT1, and LINC00565) were obtained for further lasso regression when combined with the results of drug testing and overall survival analysis. Lasso regression identified the prognostic model of ivermectin-related three-lncRNA signature (ZNRF3-AS1, SOS1-IT1, and LINC00565). The high-risk and low-risk groups based on the prognostic model were significantly related to overall survival and clinicopathologic characteristics (survival status, lymphatic invasion, cancer status, and clinical stage) in OC patients and remained independent risk factors according to multivariate COX analysis (p < 0.05). CONCLUSION Those findings provided the potential targeted lncRNA-EIF4A3-mRNA pathways of ivermectin in OC, and constructed the effective prognostic model, which benefits discovery of novel mechanism of ivermectin to suppress ovarian cancer cells, and the ivermectin-related molecule-panel changes benefit for its personalized drug therapy and prognostic assessment towards its predictive, preventive, and personalized medicine (PPPM) in OCs.
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Affiliation(s)
- Na Li
- University Creative Research Initiatives Center, Shandong First Medical University, 6699 Qingdao Road, Jinan, 250117 Shandong People’s Republic of China
- Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People’s Republic of China
- State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People’s Republic of China
| | - Xianquan Zhan
- University Creative Research Initiatives Center, Shandong First Medical University, 6699 Qingdao Road, Jinan, 250117 Shandong People’s Republic of China
- Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People’s Republic of China
- State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People’s Republic of China
- Department of Oncology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People’s Republic of China
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25
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Salamini-Montemurri M, Lamas-Maceiras M, Barreiro-Alonso A, Vizoso-Vázquez Á, Rodríguez-Belmonte E, Quindós-Varela M, Cerdán ME. The Challenges and Opportunities of LncRNAs in Ovarian Cancer Research and Clinical Use. Cancers (Basel) 2020; 12:E1020. [PMID: 32326249 PMCID: PMC7225988 DOI: 10.3390/cancers12041020] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 04/15/2020] [Accepted: 04/17/2020] [Indexed: 12/24/2022] Open
Abstract
Ovarian cancer is one of the most lethal gynecological malignancies worldwide because it tends to be detected late, when the disease has already spread, and prognosis is poor. In this review we aim to highlight the importance of long non-coding RNAs (lncRNAs) in diagnosis, prognosis and treatment choice, to make progress towards increasingly personalized medicine in this malignancy. We review the effects of lncRNAs associated with ovarian cancer in the context of cancer hallmarks. We also discuss the molecular mechanisms by which lncRNAs become involved in cellular physiology; the onset, development and progression of ovarian cancer; and lncRNAs' regulatory mechanisms at the transcriptional, post-transcriptional and post-translational stages of gene expression. Finally, we compile a series of online resources useful for the study of lncRNAs, especially in the context of ovarian cancer. Future work required in the field is also discussed along with some concluding remarks.
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Affiliation(s)
- Martín Salamini-Montemurri
- EXPRELA Group, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía, Facultade de Ciencias, INIBIC-Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain; (M.S.-M.); (M.L.-M.); (A.B.-A.); (E.R.-B.)
| | - Mónica Lamas-Maceiras
- EXPRELA Group, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía, Facultade de Ciencias, INIBIC-Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain; (M.S.-M.); (M.L.-M.); (A.B.-A.); (E.R.-B.)
| | - Aida Barreiro-Alonso
- EXPRELA Group, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía, Facultade de Ciencias, INIBIC-Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain; (M.S.-M.); (M.L.-M.); (A.B.-A.); (E.R.-B.)
| | - Ángel Vizoso-Vázquez
- EXPRELA Group, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía, Facultade de Ciencias, INIBIC-Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain; (M.S.-M.); (M.L.-M.); (A.B.-A.); (E.R.-B.)
| | - Esther Rodríguez-Belmonte
- EXPRELA Group, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía, Facultade de Ciencias, INIBIC-Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain; (M.S.-M.); (M.L.-M.); (A.B.-A.); (E.R.-B.)
| | - María Quindós-Varela
- Translational Cancer Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Carretera del Pasaje s/n, 15006 A Coruña, Spain;
| | - María Esperanza Cerdán
- EXPRELA Group, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía, Facultade de Ciencias, INIBIC-Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain; (M.S.-M.); (M.L.-M.); (A.B.-A.); (E.R.-B.)
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26
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Li T, Xing Y, Yang F, Sun Y, Zhang S, Wang Q, Zhang W. LncRNA SNHG3 sponges miR-577 to up-regulate SMURF1 expression in prostate cancer. Cancer Med 2020; 9:3852-3862. [PMID: 32248648 PMCID: PMC7286463 DOI: 10.1002/cam4.2992] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 02/25/2020] [Accepted: 03/02/2020] [Indexed: 12/14/2022] Open
Abstract
Prostate cancer remains one of the most prevalent cancers and the main causes of cancer-related deaths in males. Various articles introduced that long noncoding RNAs (lncRNAs) are found in vital functions in the development and progression of cancers. Although SNHG3 (small nucleolar RNA host gene 3) has been investigated in many cancers, now researches on the role and mechanism of SNHG3 in prostate cancer are lacked. In this work, SNHG3 exerted high expression in prostate cancer cell lines. Suppression of SNHG3 inhibited cell proliferation, migration, EMT (epithelial-mesenchymal transition) process and promoted cell apoptosis. Additionally, it was found that SNHG3 could bind with miR-577. Subsequently, SMURF1 (Smad ubiquitination regulatory factor 1) was identified as a downstream target of miR-577 and had a negative correlation with miR-577. SNHG3 was found to positively regulate SMURF1 expression. Furthermore, rescue assays demonstrated that co-transfection of pcDNA3.1/SMURF1 reversed the effects of SNHG3 knockdown in cell proliferation, migration, EMT process and cell apoptosis. SNHG3 also promoted tumorigenesis in vivo. All the results above explained that SNHG3 accelerated prostate cancer progression by sponging miR-577 to up-regulate SMURF1 expression, suggesting that SNHG3 may act as a biomarker for prostate cancer patients.
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Affiliation(s)
- Teng Li
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yi Xing
- Department of Opthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Fan Yang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yangyang Sun
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shaojin Zhang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qingwei Wang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Weixing Zhang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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27
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Duan Y, Wang Z, Xu L, Sun L, Song H, Yin H, He F. lncRNA SNHG3 acts as a novel Tumor Suppressor and regulates Tumor Proliferation and Metastasis via AKT/mTOR/ERK pathway in Papillary Thyroid Carcinoma. J Cancer 2020; 11:3492-3501. [PMID: 32284745 PMCID: PMC7150443 DOI: 10.7150/jca.42070] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 01/19/2020] [Indexed: 12/11/2022] Open
Abstract
The incidence of papillary thyroid carcinoma (PTC) has been increased rapidly in recent decades. Long noncoding RNAs (lncRNA) are a class of non-protein-coding transcripts and play critical roles in regulating gene expression and influence biological behaviors of multiple cancers, including PTC. Here, we discovered that lncRNA SNHG3 was significantly downregulated in PTC tissues and cell lines, the expression of SNHG3 was negatively correlated with the TNM stage and poor prognosis of PTC patients. Functional studies illustrated that the depletion of SNHG3 via CRISPR/Cas9 technology promoted the proliferation, migration and invasion abilities of PTC cells. Tumor xenograft models confirmed the tumor-promoting role of silenced SNHG3 in vivo. Further mechanistic analyses revealed that knockout of SNHG3 activated the AKT/mTOR/ERK pathway in PTC cell lines and the mTOR inhibitor AZD8055 abrogated the tumor-promoting effect induced by SNHG3 inhibition. Taken together, our findings identified a lncRNA SNHG3 that functions its tumor-suppressor role during PTC development and SNHG3 might serve as a promising candidate for target therapy of PTC.
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Affiliation(s)
- Yu Duan
- Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China
| | - Zhiyong Wang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China
| | - Lijuan Xu
- Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China
| | - Li Sun
- Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China
| | - Hairong Song
- Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China
| | - Huiqing Yin
- Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China
| | - Fucheng He
- Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China
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28
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Yang W, Zhang K, Li L, Ma K, Hong B, Gong Y, Gong K. Discovery and validation of the prognostic value of the lncRNAs encoding snoRNAs in patients with clear cell renal cell carcinoma. Aging (Albany NY) 2020; 12:4424-4444. [PMID: 32126023 PMCID: PMC7093172 DOI: 10.18632/aging.102894] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 02/25/2020] [Indexed: 12/11/2022]
Abstract
Some lncRNAs can encode small nucleolar RNAs (snoRNAs), called small nucleolar RNA host genes (SNHGs), which have exerted certain predictive values for the prognosis of some cancer patients. In this study, using RNA-seq and survival data in TCGA-KIRC, we examined the expression profile of 20 SNHGs and explored their prognostic values in ccRCC. Results showed that SNHG1, GAS5, SNHG3-8, SNHG11, SNHG12, SNHG15-17, SNHG20, SNHG22 and SNHG25 were significantly upregulated in ccRCC tissues compared with adjacent normal tissues. After adjustment for confounding factors, the multivariate analysis confirmed that increased SNHG3 expression was independently associated with shorter OS, while increased SNHG15 expression was an independent predictor of shorter RFS. Using the methylation data, the methylation status of 2 CpG sites (cg07807470 and cg15161854) and 2 CpG sites (cg00953154 and cg16459265) were negatively correlated with SNHG3 and SNHG15 expression, respectively. Moreover, low methylation levels of the 4 CpG sites were significantly associated with shorter OS. Furthermore, we validated the expression patterns, methylation status and prognostic value of SNHG3 and SNHG15 using clinical ccRCC samples. Taken together, SNHG3 and SNHG15 might be valuable prognostic markers in ccRCC, and DNA hypomethylation might play an important role in elevated SNHG3 and SNHG15 transcription in ccRCC.
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Affiliation(s)
- Wuping Yang
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
| | - Kenan Zhang
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
| | - Lei Li
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
| | - Kaifang Ma
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
| | - Baoan Hong
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
| | - Yanqing Gong
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
| | - Kan Gong
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
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29
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Jiao Y, Li Y, Jia B, Chen Q, Pan G, Hua F, Liu Y. The prognostic value of lncRNA SNHG4 and its potential mechanism in liver cancer. Biosci Rep 2020; 40:BSR20190729. [PMID: 31967298 PMCID: PMC6997108 DOI: 10.1042/bsr20190729] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 01/01/2020] [Accepted: 01/20/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND AND OBJECT Emerging evidence shows that non-coding RNA functions as new gene regulators and prognostic markers in several cancers, including liver cancer. Here, we focused on the small nucleolar RNA host gene 4 (SNHG4) in liver cancer prognosis based on The Cancer Genome Atlas (TCGA) data. METHODS The expression data and clinical information were downloaded from TCGA. Chi-square tests evaluated the correlation between SNHG4 expression and clinical parameters. Differences in survival between high and low expression groups (optic cutoff value determined by ROC) from Cox regression analysis were compared, and P-value was calculated by a log-rank test. Kaplan-Meier curves were compared with the log-rank test. GSEA and ceRNA network were conducted to explore the potential mechanism. RESULTS Data mining of lncRNA expression data for 371 patients with primary tumor revealed overexpression of SNHG4 in liver cancer. High SNHG4 expression was correlated with histological type (P = 0.01), histologic grade (P = 0.001), stage (P = 0.01), T classification (P = 0.004) and survival status (P = 0.013). Patients with high SNHG4 expression had poor overall survival and relapse-free survival compared with those with low SNHG4 expression. Multivariate analysis identified SNHG4 as an independent prognostic factor of poor survival in liver cancer. GSEA revealed related signaling pathway and ceRNA network explored the further mechanism. CONCLUSION High SNHG4 expression is an independent predictor of poor prognosis in liver cancer.
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Affiliation(s)
- Yan Jiao
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Yanqing Li
- Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Baoxing Jia
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Qingmin Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Guoqiang Pan
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, P.R. China
| | - Fang Hua
- Cardiovascular Internal Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Yahui Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
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30
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Abildgaard C, Do Canto LM, Steffensen KD, Rogatto SR. Long Non-coding RNAs Involved in Resistance to Chemotherapy in Ovarian Cancer. Front Oncol 2020; 9:1549. [PMID: 32039022 PMCID: PMC6985280 DOI: 10.3389/fonc.2019.01549] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 12/20/2019] [Indexed: 12/26/2022] Open
Abstract
Ovarian cancer (OC) accounts for more than 150,000 deaths worldwide every year. Patients are often diagnosed at an advanced stage with metastatic dissemination. Although platinum- and taxane-based chemotherapies are effective treatment options, they are rarely curative and eventually, the disease will progress due to acquired resistance. Emerging evidence suggests a crucial role of long non-coding RNAs (lncRNAs) in the response to therapy in OC. Transcriptome profiling studies using high throughput approaches have identified differential expression patterns of lncRNAs associated with disease recurrence. Furthermore, several aberrantly expressed lncRNAs in resistant OC cells have been related to increased cell division, improved DNA repair, up-regulation of drug transporters or reduced susceptibility to apoptotic stimuli, supporting their involvement in acquired resistance. In this review, we will discuss the key aspects of lncRNAs associated with the development of resistance to platinum- and taxane-based chemotherapy in OC. The molecular landscape of OC will be introduced, to provide a background for understanding the role of lncRNAs in the acquisition of malignant properties. We will focus on the interplay between lncRNAs and molecular pathways affecting drug response to evaluate their impact on treatment resistance. Additionally, we will discuss the prospects of using lncRNAs as biomarkers or targets for precision medicine in OC. Although there is still plenty to learn about lncRNAs and technical challenges to be solved, the evidence of their involvement in OC and the development of acquired resistance are compelling and warrant further investigation for clinical applications.
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Affiliation(s)
- Cecilie Abildgaard
- Department of Clinical Genetics, Lillebaelt Hospital-University Hospital of Southern Denmark, Vejle, Denmark.,Department of Clinical Oncology, Lillebaelt Hospital-University Hospital of Southern Denmark, Vejle, Denmark.,Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark
| | - Luisa M Do Canto
- Department of Clinical Genetics, Lillebaelt Hospital-University Hospital of Southern Denmark, Vejle, Denmark
| | - Karina D Steffensen
- Department of Clinical Oncology, Lillebaelt Hospital-University Hospital of Southern Denmark, Vejle, Denmark.,Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark
| | - Silvia R Rogatto
- Department of Clinical Genetics, Lillebaelt Hospital-University Hospital of Southern Denmark, Vejle, Denmark.,Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark
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31
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Liu Z, Tao H. Small nucleolar RNA host gene 3 facilitates cell proliferation and migration in oral squamous cell carcinoma via targeting nuclear transcription factor Y subunit gamma. J Cell Biochem 2019; 121:2150-2158. [PMID: 31762107 DOI: 10.1002/jcb.29421] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 10/08/2019] [Indexed: 12/15/2022]
Abstract
Oral squamous cell carcinoma (OSCC) has been reported to be the most common oral carcinoma. Emerging evidence has revealed the key role that long noncoding RNAs (lncRNAs) play in numerous malignancies, including OSCC. LncRNA small nucleolar RNA host gene 3 (SNHG3) has been reported as an oncogenic factor in some cancers. Nonetheless, the role of SNHG3 in OSCC has never been clarified. In this study, we analyzed the expression patterns of SNHG3 in OSCC through quantitative real-time polymerase chain reaction. It was revealed that the expression level of SNHG3 was remarkably elevated in OSCC cell lines compared with the nontumor cell line. It was demonstrated by functional experiments that SNHG3 knockdown notably inhibited cell proliferation and migration in OSCC. RNA immunoprecipitation, RNA pull down, and messenger RNA (mRNA) stability test verified that SNHG3 decoyed ELAV like RNA-binding protein 1 (ELAVL1) and therefore stabilized nuclear transcription factor Y subunit gamma (NFYC) mRNA to upregulate the expression levels of NFYC in OSCC cells. At last, it was confirmed by rescue experiments that the inhibiting impacts of SNHG3 knockdown on OSCC cell proliferation and migration could be partly revived by NFYC overexpression. Besides, we validated that Wnt/β-catenin pathway was also involved in SNHG3-regulated OSCC progression. In conclusion, SNHG3 might serve as a novel biomarker for OSCC.
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Affiliation(s)
- Zhi Liu
- Department of Oral, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi, China
| | - Hong Tao
- Department of Oral, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi, China
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32
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Shi J, Li J, Yang S, Hu X, Chen J, Feng J, Shi T, He Y, Mei Z, He W, Xie J, Li S, Jie Z, Tu S. LncRNA SNHG3 is activated by E2F1 and promotes proliferation and migration of non-small-cell lung cancer cells through activating TGF-β pathway and IL-6/JAK2/STAT3 pathway. J Cell Physiol 2019; 235:2891-2900. [PMID: 31602642 DOI: 10.1002/jcp.29194] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 09/03/2019] [Indexed: 12/15/2022]
Abstract
Recently, long noncoding RNAs (lncRNAs) have been widely reported to play pivotal roles in the regulation of human cancers. Although the oncogenic property of lncRNA small nucleolar RNA host gene 3 (SNHG3) has been revealed in a variety of cancers, functions and regulatory mechanism of SNHG3 in non-small-cell lung cancer (NSCLC) remain to be investigated. In this study, we detected the upregulated expression of SNHG3 in NSCLC tissues as well as cells through quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. Using Kaplan-Meier analysis, we determined that a high-level of SNHG3 was associated with a low overall survival rate of patients with NSCLC. Through gain and loss of function experiments, we demonstrated that SNHG3 had a significantly positive effect on NSCLC cell proliferation and migration. Mechanistic investigations revealed that SNHG3 was a predicted direct transcriptional target of E2F1. We observed that the transcriptional activation of SNHG3 could be induced by E2F1. To explore the mechanism, rescue experiments were carried out, which revealed that the cotreatment with SB-431542, JSI-124, or JSI-124 + SB-431542 rescued the effects brought by the overexpression of SNHG3 on NSCLC cell proliferation, migration, and epithelial-mesenchymal transition process. Our results suggested that E2F1 activated SNHG3 and promoted cell proliferation and migration in NSCLC via transforming growth factor-β pathway and interleukin-6/janus-activated kinase 2/signal transducer and activator of transcription 3 pathway, which implied that SNHG3 may be a biomarker for the treatment of patients with NSCLC.
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Affiliation(s)
- Jindong Shi
- Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Jiannan Li
- Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Shuang Yang
- General Department, Jiangchuan Community Healthcare Service Center, Shanghai, China
| | - Xiaoying Hu
- General Department, Jiangchuan Community Healthcare Service Center, Shanghai, China
| | - Jiajun Chen
- Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Jingjing Feng
- Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Tianyun Shi
- Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Yanchao He
- Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Zhoufang Mei
- Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Wei He
- Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Juan Xie
- Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Shanqun Li
- Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhijun Jie
- Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Shuiping Tu
- Department of Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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33
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Ma Q, Qi X, Lin X, Li L, Chen L, Hu W. LncRNA SNHG3 promotes cell proliferation and invasion through the miR-384/hepatoma-derived growth factor axis in breast cancer. Hum Cell 2019; 33:232-242. [DOI: 10.1007/s13577-019-00287-9] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 09/27/2019] [Indexed: 12/14/2022]
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34
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Long non-coding RNA SNHG3 promotes progression of gastric cancer by regulating neighboring MED18 gene methylation. Cell Death Dis 2019; 10:694. [PMID: 31534128 PMCID: PMC6751301 DOI: 10.1038/s41419-019-1940-3] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 08/15/2019] [Accepted: 08/26/2019] [Indexed: 12/21/2022]
Abstract
To understand the mechanistic involvement of long non-coding RNA (lncRNA) SNHG3 in gastric cancer (GC), the relative abundance of SNHG3 was determined by real-time PCR. Overall and metastasis-free survival was analyzed by Kaplan–Meier’s plot. The potential impact of SNHG3 on tumor progression was evaluated both in vitro and in vivo. The in vivo metastasis was monitored in the tail vein-injected mice. Our data suggested that high SNHG3 associated with unfavorable prognosis in respect to overall and metastasis-free survival. SNHG3-deficiency significantly suppressed cell proliferation and cell viability in vitro and xenograft progression in vivo. In addition, ectopic overexpression of SNHG3 promoted cell migration and invasion in vitro and lung metastasis in vivo. Mechanistically, we uncovered SNHG3 associated with EZH2 and negatively regulated MED18 expression through methylation modulation. Transient knockdown of MED18 in SNHG3-deficient cells completely rescued the tumor suppressive phenotypes in GC cells. Our data unraveled the oncogenic properties of high SNHG3 in GC, which predominantly depended on epigenetically regulated MED18.
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Peng L, Zhang Y, Xin H. lncRNA SNHG3 facilitates acute myeloid leukemia cell growth via the regulation of miR-758-3p/SRGN axis. J Cell Biochem 2019; 121:1023-1031. [PMID: 31452272 DOI: 10.1002/jcb.29336] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 04/11/2019] [Indexed: 12/14/2022]
Abstract
Small nucleolar RNA host gene 3 (SNHG3) is a newly identified long non-coding RNA whose dysregulation has been reported in several cancers. However, the details about clinical significances and biological functions of SNHG3 on acute myeloid leukemia (AML) remain covered. In this study, we revealed increased SNHG3 expression in AML samples and cells and its high potential as a prognostic biomarker for AML patients. Likewise, serglycin (SRGN), which plays an important role in granule-mediated apoptosis, was previously verified to be upregulated in AML and confirmed again by the present study, and its upregulation predicted poor outcomes in AML. Furthermore, knockdown of SNHG3 or SRGN inhibited cell proliferation and induced cell apoptosis. Besides, silencing SNHG3 noticeably decreased the expression of SRGN in AML cells. Moreover, we uncovered that SNHG3 modulated SRGN expression by competitively binding with miR-758-3p. Importantly, both miR-758-3p suppression and SRGN overexpression could mitigate the inhibitory effects of SNHG3 depletion on AML cell growth. Intriguingly, the higher SRGN expression in AML samples with a higher SNHG3 level exhibited an enhanced Ki67 level but a reduced caspase 3 level. To sum up, SNHG3 elicits a growth-promoting function in AML via sponging miR-758-3p to regulate SRGN expression, providing a new therapeutic road for AML patients.
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Affiliation(s)
- Linqiang Peng
- Department of Pediatrics, Baoji People's Hospital Shaanxi Province, Baoji, Shaanxi, China
| | - Yanzhi Zhang
- Department of Pediatrics, Lanling County People's Hospital, Lanling, Shandong, China
| | - Hongli Xin
- Department of Pediatrics, Lanling County People's Hospital, Lanling, Shandong, China
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36
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Chen J, Wu Z, Zhang Y. LncRNA SNHG3 promotes cell growth by sponging miR-196a-5p and indicates the poor survival in osteosarcoma. Int J Immunopathol Pharmacol 2019; 33:2058738418820743. [PMID: 30791797 PMCID: PMC6329016 DOI: 10.1177/2058738418820743] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Abnormal expression of long noncoding RNAs (lncRNAs) is closely associated with the pathogenesis of multiple malignancies, and lncRNA small nucleolar RNA host genes (SNHGs) play critical roles in tumor progression. However, the mechanism by which SNHG3 contributes to osteosarcoma (OS) remains elusive. The association between SNHG3 expression and the clinicopathological characteristics in OS patients was analyzed using the TCGA (The Cancer Genome Atlas) dataset. Cell viability and colony number were estimated by MTT and colony formation assays. MiR-196a-5p-specific binding with SNHG3 or HOXC8 was confirmed by the luciferase report assay. As a result, the expression of SNHG3 was dramatically increased in OS tissue as compared with the adjacent normal tissues. High expression of SNHG3 was associated with tumor size and acted as an independent prognostic factor of poor survival in OS patients. Knockdown of SNHG3 inhibited cell viability and colony formation, but its overexpression reversed these effects. SNHG3 was further identified to act as a sponge of miR-196a-5p, which counteracted the tumor-promoting effects caused by SNHG3 in OS cells. The expression of miR-196a-5p had a negative correlation with SNHG3 and the poor survival in OS patients. In conclusion, lncRNA SNHG3 promoted cell growth by sponging miR-196a-5p and indicated a poor prognosis in OS patients.
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Affiliation(s)
- Jun Chen
- 1 Department of Orthopedic Surgery, Jing'an District Zhabei Central Hospital, Shanghai, China
| | - Zhouyi Wu
- 1 Department of Orthopedic Surgery, Jing'an District Zhabei Central Hospital, Shanghai, China
| | - Yong Zhang
- 2 Department of Orthopedic Surgery, Shibei Hospital of Jingan District, Shanghai, China
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Lu W, Yu J, Shi F, Zhang J, Huang R, Yin S, Songyang Z, Huang J. The long non-coding RNA Snhg3 is essential for mouse embryonic stem cell self-renewal and pluripotency. Stem Cell Res Ther 2019; 10:157. [PMID: 31151411 PMCID: PMC6545032 DOI: 10.1186/s13287-019-1270-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 05/08/2019] [Accepted: 05/20/2019] [Indexed: 02/07/2023] Open
Abstract
Background Small nucleolar RNA host gene 3 (Snhg3) is a long non-coding RNA (lncRNA) that was shown to participate in the tumorigenesis of certain cancers. However, little is known about its role in embryonic stem cells (ESCs). Methods Here, we investigated the role of Snhg3 in mouse ESCs (mESCs) through both loss-of-function (knockdown) and gain-of-function (overexpression) approaches. Alkaline phosphatase staining, secondary colony formation, propidium iodide staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to access self-renewal capacity, whereas immunofluorescence, qRT-PCR, and embryoid body formation were performed to examine pluripotency. In addition, the effect of Snhg3 on mouse embryonic development was determined based on the morphological changes, blastocyst rate, and altered pluripotency marker (Nanog, Oct4) expression. Moreover, the relationship between Snhg3 and key pluripotency factors was evaluated by chromatin immunoprecipitation qPCR, qRT-PCR, subcellular fractionation, and RNA immunoprecipitation. Finally, RNA pull-down and mass spectrometry were applied to explore the potential interacting proteins of Snhg3 in mESCs. Results We demonstrated that Snhg3 is essential for self-renewal and pluripotency maintenance in mESCs. In addition, Snhg3 knockdown disrupted mouse early embryo development. Mechanistically, Snhg3 formed a positive feedback network with Nanog and Oct4, and 126 Snhg3-interacting proteins were identified in mESCs. Conclusions Snhg3 is essential for mESC self-renewal and pluripotency, as well as mouse early embryo development. Electronic supplementary material The online version of this article (10.1186/s13287-019-1270-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Weisi Lu
- The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
| | - Jianping Yu
- MOE Key Laboratory of Gene Function and Regulation, Guangzhou Key Laboratory of Healthy Aging Research and State Key Laboratory of Biocontrol, SYSU-BCM Joint Research Center, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China
| | - Fengtao Shi
- Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, V5Z 4E8, Canada
| | - Jianing Zhang
- The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China
| | - Rui Huang
- Verna and Marrs Mclean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA
| | - Shanshan Yin
- MOE Key Laboratory of Gene Function and Regulation, Guangzhou Key Laboratory of Healthy Aging Research and State Key Laboratory of Biocontrol, SYSU-BCM Joint Research Center, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China
| | - Zhou Songyang
- The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China. .,MOE Key Laboratory of Gene Function and Regulation, Guangzhou Key Laboratory of Healthy Aging Research and State Key Laboratory of Biocontrol, SYSU-BCM Joint Research Center, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China. .,Verna and Marrs Mclean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
| | - Junjiu Huang
- The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China. .,MOE Key Laboratory of Gene Function and Regulation, Guangzhou Key Laboratory of Healthy Aging Research and State Key Laboratory of Biocontrol, SYSU-BCM Joint Research Center, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
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38
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Zhu Q, Yang H, Cheng P, Han Q. Bioinformatic analysis of the prognostic value of the lncRNAs encoding snoRNAs in hepatocellular carcinoma. Biofactors 2019; 45:244-252. [PMID: 30537372 DOI: 10.1002/biof.1478] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 10/24/2018] [Accepted: 10/25/2018] [Indexed: 12/14/2022]
Abstract
Some lncRNAs can encode small nucleolar RNAs (snoRNAs), called small nucleolar RNA host genes (SNHGs), which exert diverse regulatory effects on cellular processes. In this study, using RNA-seq and survival data in the Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma (LIHC), we examined the expression profile of some SNHG genes and explored their prognostic value in hepatocellular carcinoma (HCC). Level-3 RNA-sequencing data, the clinicopathological and survival data of patients with primary HCC were downloaded from the UCSC Xena browser (https://xenabrowser.net/), for a secondary analysis. Results showed that SNHG1, GAS5, SNHG3-7 and SNHG10-12 were significantly upregulated in HCC tissues (N = 49) compared with adjacent normal tissues (N = 49). After adjustment for confounding factors, the multivariate analysis confirmed that increased SNHG4 expression was independently associated with shorter OS (HR: 1.319, 95%CI: 1.131-1.537, P < 0.001), while increased GAS5 expression was an independent predictor of shorter RFS (HR: 1.287, 95% CI: 1.027-1.612, P = 0.028). Using the methylation data obtained from the Infinium HumanMethylation450 BeadChip, we found that SNHG4 expression was not likely to be modulated by methylation in HCC. In comparison, the methylation status of 5 CpG sites (cg07177756, cg17025683, cg16290996, cg03044573 and cg06644515) showed a moderately negative correlation (Pearson's r = -0.54, P < 0.001) with GAS5 expression. Based on these findings, we infer that SNHG4 and GAS5 might be valuable prognostic markers in HCC. DNA hypomethylation might play an important role in elevated GAS5 transcription in HCC. © 2018 BioFactors, 45(2):244-252, 2019.
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Affiliation(s)
- Qingyao Zhu
- Department of Oncology Radiotherapy, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Hongjie Yang
- Department of Oncology Radiotherapy, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Peng Cheng
- Department of Oncology Radiotherapy, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Qian Han
- Department of Oncology Radiotherapy, Henan Provincial People's Hospital, Zhengzhou, Henan, China
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