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Ding Z, Hou Z, Zhang T, Wang P, Pan X, Li X, Zhao S. FKBP Prolyl Isomerase 11: A Novel Oncogene Interacting With SRSF1 in Esophageal Squamous Cell Carcinoma. Mol Carcinog 2025; 64:638-651. [PMID: 39775874 DOI: 10.1002/mc.23877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 11/12/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025]
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the main subtypes of esophageal carcinoma with high morbidity. This study aimed to explore the role of FKBP prolyl isomerase 11 (FKBP11) in ESCC and investigate the underlying mechanism. FKBP11 levels in ESCC tumor tissues and cell lines were measured. Cell function assays were conducted to evaluate the role of FKBP11 in ESCC cells. The xenograft mouse model was established to validate the effect of FKBP11 on ESCC tumorigenesis in vivo. The co-immunoprecipitation assay was performed to determine the FKBP11-interacting proteins. Obvious upregulations in FKBP11 expression were found in ESCC tumor tissues and cell lines. In vitro, FKBP11 knockdown weakened cell proliferation, migration, and invasion capacities and reinforced cell apoptosis in ESCC cells. In vivo, FKBP11 knockdown slowed ESCC tumorigenesis. The following mechanism investigation determined serine and arginine-rich splicing factor 1 (SRSF1) as the FKBP11-interacting protein in ESCC cells. FKBP11 directly bound to SRSF1 and FKBP11 knockdown decreased SRSF1 mRNA level. SRSF1 overexpression abrogated the inhibitory effect of FKBP11 knockdown on the proliferation and migration of ESCC cells. KBP11 functions as an oncogene in ESCC by targeting SRSF1.
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Affiliation(s)
- Zheng Ding
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, ZhengZhou, China
| | - Zhichao Hou
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, ZhengZhou, China
| | - Tangjuan Zhang
- Department of Emergency, The First Affiliated Hospital of Zhengzhou University, ZhengZhou, China
| | - Peng Wang
- School of Nursing and Health, Zhengzhou University, ZhengZhou, China
| | - Xue Pan
- School of Nursing and Health, Zhengzhou University, ZhengZhou, China
| | - Xiangnan Li
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, ZhengZhou, China
| | - Song Zhao
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, ZhengZhou, China
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Cheng Y, Dang S, Zhang Y, Chen Y, Yu R, Liu M, Jin S, Han A, Katz S, Wang S. Sequencing-free whole genome spatial transcriptomics at molecular resolution in intact tissue. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.03.06.641951. [PMID: 40161724 PMCID: PMC11952344 DOI: 10.1101/2025.03.06.641951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Recent breakthroughs in spatial transcriptomics technologies have enhanced our understanding of diverse cellular identities, compositions, interactions, spatial organizations, and functions. Yet existing spatial transcriptomics tools are still limited in either transcriptomic coverage or spatial resolution. Leading spatial-capture or spatial-tagging transcriptomics techniques that rely on in-vitro sequencing offer whole-transcriptome coverage, in principle, but at the cost of lower spatial resolution compared to image-based techniques. In contrast, high-performance image-based spatial transcriptomics techniques, which rely on in situ hybridization or in situ sequencing, achieve single-molecule spatial resolution and retain sub-cellular morphologies, but are limited by probe libraries that target only a subset of the transcriptome, typically covering several hundred to a few thousand transcript species. Together, these limitations hinder unbiased, hypothesis-free transcriptomic analyses at high spatial resolution. Here we develop a new image-based spatial transcriptomics technology termed Reverse-padlock Amplicon Encoding FISH (RAEFISH) with whole-genome level coverage while retaining single-molecule spatial resolution in intact tissues. We demonstrate image-based spatial transcriptomics targeting 23,000 human transcript species or 22,000 mouse transcript species, including nearly the entire protein-coding transcriptome and several thousand long-noncoding RNAs, in single cells in cultures and in tissue sections. Our analyses reveal differential subcellular localizations of diverse transcripts, cell-type-specific and cell-type-invariant tissue zonation dependent transcriptome, and gene expression programs underlying preferential cell-cell interactions. Finally, we further develop our technology for direct spatial readout of gRNAs in an image-based high-content CRISPR screen. Overall, these developments provide the research community with a broadly applicable technology that enables high-coverage, high-resolution spatial profiling of both long and short, native and engineered RNA species in many biomedical contexts.
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Affiliation(s)
- Yubao Cheng
- Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Shengyuan Dang
- Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
- These authors contributed equally to this work
| | - Yuan Zhang
- Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
- These authors contributed equally to this work
| | - Yanbo Chen
- Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Ruihuan Yu
- Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
- Present Address: Department of Biological Sciences, Columbia University, New York, NY 10027, USA
| | - Miao Liu
- Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Shengyan Jin
- Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Ailin Han
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Samuel Katz
- Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Siyuan Wang
- Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
- M.D.-Ph.D. Program, Yale University, New Haven, CT 06510, USA
- Yale Combined Program in the Biological and Biomedical Sciences, Yale University, New Haven, CT 06510, USA
- Molecular Cell Biology, Genetics and Development Program, Yale University, New Haven, CT 06510, USA
- Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA
- Biochemistry, Quantitative Biology, Biophysics, and Structural Biology Program, Yale University, New Haven, CT 06510, USA
- Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
- Yale Liver Center, Yale University School of Medicine, New Haven, CT 06510, USA
- Lead contact
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Gao L, Huang J, Xia J, Zhao P, Dong S, Jiang W, Zhou Q, Xu Z, Luo H, Zhou W, Sun J, Wang G, Geng Q, Wang J, Zou C. SNHG17 Reprograms Energy Metabolism of Breast Cancer by Activating Mitochondrial DNA Transcription. Cancer Res 2025; 85:1097-1112. [PMID: 39841089 DOI: 10.1158/0008-5472.can-24-1271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 08/21/2024] [Accepted: 01/08/2025] [Indexed: 01/23/2025]
Abstract
In most solid tumors, cellular energy metabolism is primarily dominated by aerobic glycolysis, which fulfills the high demand for biomacromolecules at the expense of reduced ATP production efficiency. Elucidation of the mechanisms by which rapidly proliferating malignant cells acquire sufficient energy in this state of inefficient ATP production from glycolysis could enable the development of metabolism-targeted therapeutic strategies. In this study, we observed a significant association between elevated expression levels of the long noncoding RNA small nuclear RNA host gene 17 (SNHG17) and unfavorable prognosis in breast cancer. SNHG17 promoted breast cancer cell proliferation by augmenting mitochondrial ATP production. Mechanistically, SNHG17 directly interacted with the P65 subunit of NF-κB and phosphorylated P65 at the threonine 505 site. SNHG17 bound to P65 at its truncated loop2 site, recruited P65 to mitochondria, and coregulated the transcriptional activation of mitochondrial DNA to promote ATP production. Accordingly, targeting SNHG17 with an antisense oligonucleotide significantly reduced breast cancer tumor growth both in vitro and in vivo. Overall, these results established a role for SNHG17 in promoting breast cancer progression by increasing ATP production and provided insights into the reprogramming of energy metabolism in solid tumors. Significance: SNHG17 cooperates with NF-κB to induce expression of mitochondrial DNA and boost ATP production in breast cancer, suggesting that targeting SNHG17 could reverse metabolic reprogramming to suppress tumor progression.
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Affiliation(s)
- Lin Gao
- Department of Thoracic Surgery, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
| | - Jingyi Huang
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
| | - Jinquan Xia
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
| | - Pan Zhao
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
- Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis, the Second Clinical Medical College, Jinan University, Shenzhen, P.R. China
| | - Shaowei Dong
- Department of Hematology and Oncology, Shenzhen Children's Hospital of China Medical University, Shenzhen, P.R. China
| | - Wei Jiang
- Department of Breast Surgery, Harbin Medical University, Harbin, P.R. China
| | - Qianqian Zhou
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
| | - Zhenglei Xu
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
| | - Hui Luo
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
| | - Wenbin Zhou
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
| | - Jichao Sun
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
| | - Guangsuo Wang
- Department of Thoracic Surgery, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
| | - Qingshan Geng
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
| | - Jigang Wang
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
| | - Chang Zou
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
- Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis, the Second Clinical Medical College, Jinan University, Shenzhen, P.R. China
- School of Life and Health Sciences, The Chinese University of Kong Hong, Shenzhen, P.R. China
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Shi K, Huang LD, Li D, Luo WM, Liu HS, Ding DX, Guo Q, Liu YF. Aberrant SNHG expression predicts poor prognosis in esophageal cancer using meta-analysis and bioinformatics analysis. BMC Gastroenterol 2025; 25:63. [PMID: 39920577 PMCID: PMC11804041 DOI: 10.1186/s12876-025-03621-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 01/16/2025] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND Small nucleolar RNA host gene (SNHG) family were reported involved in various biological processes and may be used as a promising prognostic marker in esophageal cancer (EC). A meta-analysis was performed to investigate the relationship between SNHG expression and prognosis of EC in this study. METHODS Relevant databases were browsed to obtain suitable publications. Hazard ratio (HR) with 95% confidence interval (CI) were extracted to explore the association between SNHG expression and EC prognosis. Odds ratio (OR) with 95%CI were extracted to assess the association between SNHG expression and other clinicopathological parameters. Sensitivity analysis and publication bias were performed to explore the reliability and robustness of the results. Bio-informatics has been explored in order to confirm our conclusions more comprehensively. RESULTS 16 studies comprising 1229 patients were enrolled. The results showed that increasing SNHG expression indicated worse overall survival (HR: 1.392, 95%CI = 0.876-1.908). SNHG2, SNHG5, and SNHG12 were down-regulated, while other SNHGs were up-regulated in EC. In populations with low expression of SNHG2, SNHG5, and SNHG12, increasing SNHG expression predicted a favorable cancer prognosis (HR: 0.511, 95%CI = 0.322-0.700). Conversely, in populations with high expression of other SNHGs, SNHG expression indicated poor prognosis (OR: 2.340, 95%CI = 1.744-2.936). Elevated SNHG expression also implied advanced TNM stage (OR 1.578, 95%CI = 1.273-1.956) and lymph node metastasis (OR: 1.533, 95%CI = 1.205-1.950). CONCLUSION Increased expression of SNHG2, SNHG5, and SNHG12, and decreased expression of other SNHGs tended to have a favorable prognosis in patients with EC. These findings suggest that SNHG may serve as a prognostic marker and therapeutic target for EC.
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Affiliation(s)
- Ke Shi
- Department of Thoracic Surgery, Beilun District People's Hospital of Ningbo, Ningbo City, China
| | - Li-De Huang
- Department of Pain management, People's Hospital of Shiyan City, Hubei Medical University, Shiyan City, China
| | - Dan Li
- Department of Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan City, China
| | - Wei-Min Luo
- Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan City, China
| | - Hua-Song Liu
- Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan City, China
| | - Dong-Xiao Ding
- Department of Thoracic Surgery, Beilun District People's Hospital of Ningbo, Ningbo City, China.
| | - Qiang Guo
- Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan City, China.
| | - Yue-Feng Liu
- Department of Ophthalmology, Taihe Hospital, Hubei University of Medicine, Shiyan City, China.
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Zou W, Li Y, Zhang J, Yang R, Yan Y, Zhang X, Yan L, Zhang Z, Zhang X, Chen J. Cancer-associated fibroblast-derived circFARP1 modulates non-small cell lung cancer invasion and metastasis through the circFARP1/miR-338-3p/SOX4 axis. Clin Exp Pharmacol Physiol 2024; 51:e13914. [PMID: 39139001 DOI: 10.1111/1440-1681.13914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 05/13/2024] [Accepted: 05/31/2024] [Indexed: 08/15/2024]
Abstract
The pleiotropic effect of cancer-associated fibroblasts (CAFs) on tumour progression depends on the environment. circFARP1 is critical for CAFs-induced gemcitabine (GEM) resistance in pancreatic cancer. Its specific role and mechanism in non-small cell lung cancer (NSCLC) have not been reported yet. We prepared a cancer-associated fibroblasts-conditioned medium (CAF-CM) to incubate the A549 cells. Quantitative real-time polymerase chain reaction was used to detect RNA levels. We detected protein expression by immunohistochemistry, immunocytochemistry, western blot and immunofluorescence. We also detected the targeting impact between circFARP1, miR-338-3p and SRY-box transcription factor 4 (SOX4) by using dual-luciferase reporter and RNA pull-down assays. We determined cell proliferation, migration and invasion capabilities through Cell Counting Kit-8 and transwell assays. In addition, we measured tumour volume and weight in vivo by establishing a xenograft tumour model. CircFARP1 levels were remarkably high in the CAFs. The transfection experiments found that circFARP1 downregulation in CAFs caused migration, proliferation and invasion inhibition of CAFs and A549 cells, whereas inhibiting miR-38-3p or overexpressing SOX4 in CAFs could significantly reverse the inhibition. In vivo study in nude mice confirmed that CAFs could promote NSCLC tumour growth and knockdown of circFARP1 could inhibit tumour growth of NSCLC, whereas miR-38-3p downregulation or SOX4 overexpression could significantly reverse the inhibition. circFARP1 promotes NSCLC development by stimulating miR-338-3p/SOX4 signalling axis to regulate CAFs.
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Affiliation(s)
- Wailong Zou
- Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Beijing, China
| | - Yulin Li
- Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Beijing, China
| | - Jia Zhang
- Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Beijing, China
| | - Rui Yang
- Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Beijing, China
| | - Yaxin Yan
- Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Beijing, China
| | - Xin Zhang
- Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Beijing, China
| | - Lei Yan
- Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Beijing, China
| | - Zhe Zhang
- Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Beijing, China
| | - Xinjun Zhang
- Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Beijing, China
| | - Jichao Chen
- Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Beijing, China
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Yan Q, Wong W, Gong L, Yang J, Liang D, Chin KY, Dai S, Wang J. Roles of long non‑coding RNAs in esophageal cell squamous carcinoma (Review). Int J Mol Med 2024; 54:72. [PMID: 38963019 PMCID: PMC11232667 DOI: 10.3892/ijmm.2024.5396] [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] [Received: 02/24/2024] [Accepted: 06/06/2024] [Indexed: 07/05/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a prevalent and deadly malignancy of the digestive tract. Recent research has identified long non‑coding RNAs (lncRNAs) as crucial regulators in the pathogenesis of ESCC. These lncRNAs, typically exceeding 200 nucleotides, modulate gene expression through various mechanisms, including the competing endogenous RNA (ceRNA) pathway and RNA‑protein interactions. The current study reviews the multifaceted roles of lncRNAs in ESCC, highlighting their involvement in processes such as proliferation, migration, invasion, epithelial‑mesenchymal transition, cell cycle progression, resistance to radiotherapy and chemotherapy, glycolysis, apoptosis, angiogenesis, autophagy, tumor growth, metastasis and the maintenance of cancer stem cells. Specific lncRNAs like HLA complex P5, LINC00963 and non‑coding repressor of NFAT have been shown to enhance resistance to radio‑ and chemotherapy by modulating pathways such as AKT signaling and microRNA interaction, which promote cell survival and proliferation under therapeutic stress. Furthermore, lncRNAs like family with sequence similarity 83, member A antisense RNA 1, zinc finger NFX1‑type containing 1 antisense RNA 1 and taurine upregulated gene 1 are implicated in enhancing invasive and proliferative capabilities of ESCC cells through the ceRNA mechanism, while interactions with RNA‑binding proteins further influence cancer cell behavior. The comprehensive analysis underscores the potential of lncRNAs as biomarkers for prognosis and therapeutic targets in ESCC, suggesting avenues for future research focused on elucidating the detailed molecular mechanisms and clinical applications of lncRNAs in ESCC management.
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Affiliation(s)
- Qihang Yan
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong 510060, P.R. China
| | - Wingshing Wong
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Li Gong
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Jie Yang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Dachuan Liang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Kok-Yong Chin
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Malaysia
| | - Shuqin Dai
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Junye Wang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong 510060, P.R. China
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Saeinasab M, Atlasi Y, M Matin M. Functional role of lncRNAs in gastrointestinal malignancies: the peculiar case of small nucleolar RNA host gene family. FEBS J 2024; 291:1353-1385. [PMID: 36282516 DOI: 10.1111/febs.16668] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 09/18/2022] [Accepted: 10/24/2022] [Indexed: 11/06/2022]
Abstract
Long noncoding RNAs (lncRNAs) play crucial roles in normal physiology and are often de-regulated in disease states such as cancer. Recently, a class of lncRNAs referred to as the small nucleolar RNA host gene (SNHG) family have emerged as important players in tumourigenesis. Here, we discuss new findings describing the role of SNHGs in gastrointestinal tumours and summarize the three main functions by which these lncRNAs promote carcinogenesis, namely: competing with endogenous RNAs, modulating protein function, and regulating epigenetic marking. Furthermore, we discuss how SNHGs participate in different hallmarks of cancer, and how this class of lncRNAs may serve as potential biomarkers in cancer diagnosis and therapy.
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Affiliation(s)
- Morvarid Saeinasab
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Iran
| | - Yaser Atlasi
- Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, UK
| | - Maryam M Matin
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Iran
- Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Iran
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8
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Wei QY, Jin F, Wang ZY, Li BJ, Cao WB, Sun ZY, Mo SJ. MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma. World J Gastroenterol 2024; 30:1497-1523. [PMID: 38617454 PMCID: PMC11008420 DOI: 10.3748/wjg.v30.i11.1497] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/12/2024] [Accepted: 03/01/2024] [Indexed: 03/21/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.
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Affiliation(s)
- Qi-Ying Wei
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Feng Jin
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Zhong-Yu Wang
- Department of Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Bing-Jie Li
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Wen-Bo Cao
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Zhi-Yan Sun
- Division of Special Service, Department of Basic Oncology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Sai-Jun Mo
- Department of Basic Science of Oncology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
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Jiang J, Wang Y, Sun M, Luo X, Zhang Z, Wang Y, Li S, Hu D, Zhang J, Wu Z, Chen X, Zhang B, Xu X, Wang S, Xu S, Huang W, Xia L. SOX on tumors, a comfort or a constraint? Cell Death Discov 2024; 10:67. [PMID: 38331879 PMCID: PMC10853543 DOI: 10.1038/s41420-024-01834-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 01/23/2024] [Accepted: 01/25/2024] [Indexed: 02/10/2024] Open
Abstract
The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family, composed of 20 transcription factors, is a conserved family with a highly homologous HMG domain. Due to their crucial role in determining cell fate, the dysregulation of SOX family members is closely associated with tumorigenesis, including tumor invasion, metastasis, proliferation, apoptosis, epithelial-mesenchymal transition, stemness and drug resistance. Despite considerable research to investigate the mechanisms and functions of the SOX family, confusion remains regarding aspects such as the role of the SOX family in tumor immune microenvironment (TIME) and contradictory impacts the SOX family exerts on tumors. This review summarizes the physiological function of the SOX family and their multiple roles in tumors, with a focus on the relationship between the SOX family and TIME, aiming to propose their potential role in cancer and promising methods for treatment.
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Affiliation(s)
- Junqing Jiang
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Yufei Wang
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Mengyu Sun
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Xiangyuan Luo
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Zerui Zhang
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Yijun Wang
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Siwen Li
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Dian Hu
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Jiaqian Zhang
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Zhangfan Wu
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Xiaoping Chen
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases; Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Clinical Medicine Research Center for Hepatic Surgery of Hubei Province; Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, Hubei, 430030, China
| | - Bixiang Zhang
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases; Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Clinical Medicine Research Center for Hepatic Surgery of Hubei Province; Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, Hubei, 430030, China
| | - Xiao Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Shuai Wang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Westlake university school of medicine, Hangzhou, 310006, China
| | - Shengjun Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Wenjie Huang
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases; Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Clinical Medicine Research Center for Hepatic Surgery of Hubei Province; Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, Hubei, 430030, China.
| | - Limin Xia
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
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10
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Yang R, Wan J, Ma L, Zhou F, Yang Z, Li Z, Zhang M, Ming L. TMEM44-AS1 promotes esophageal squamous cell carcinoma progression by regulating the IGF2BP2-GPX4 axis in modulating ferroptosis. Cell Death Discov 2023; 9:431. [PMID: 38040698 PMCID: PMC10692126 DOI: 10.1038/s41420-023-01727-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 11/07/2023] [Accepted: 11/16/2023] [Indexed: 12/03/2023] Open
Abstract
The long non-coding RNA (lncRNA) TMEM44-AS1 is a novel lncRNA whose pro-carcinogenic role in gastric cancer and glioma has been demonstrated. However, its function in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we identified that TMEM44-AS1 was highly expressed in ESCC tissues and cells. Functionally, TMEM44-AS1 promoted ESCC cell proliferation, invasion and metastasis in vitro and in vivo. TMEM44-AS1 inhibited ferroptosis in ESCC cells, and ferroptosis levels were significantly increased after knockdown of TMEM44-AS1. Mechanistically, TMEM44-AS1 was positively correlated with GPX4 expression, and TMEM44-AS1 could bind to the RNA-binding protein IGF2BP2 to enhance the stability of GPX4 mRNA, thereby affecting ferroptosis and regulating the malignant progression of ESCC. In summary, this study reveals the TMEM44-AS1-IGF2BP2-GPX4 axis could influence cancer progression in ESCC. TMEM44-AS1 can be used as a potential treatment target against ESCC.
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Affiliation(s)
- Ruotong Yang
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Clinical Laboratory of Henan province, Zhengzhou, China
| | - Junhu Wan
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Clinical Laboratory of Henan province, Zhengzhou, China
| | - Liwei Ma
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Clinical Laboratory of Henan province, Zhengzhou, China
| | - Fuyou Zhou
- Thoracic Department, Anyang Tumor Hospital, Henan Key Medical Laboratory of Precise Prevention and Treatment of Esophageal Cancer, Anyang, China
| | - Zhengwu Yang
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Clinical Laboratory of Henan province, Zhengzhou, China
| | - Zhuofang Li
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Clinical Laboratory of Henan province, Zhengzhou, China
| | - Mingyuan Zhang
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Clinical Laboratory of Henan province, Zhengzhou, China
| | - Liang Ming
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
- Key Clinical Laboratory of Henan province, Zhengzhou, China.
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11
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Dai S, Zhang C, Wei X, Wang X, Wen Y, Gao F, Zhao L, Shan B. RNA sequencing reveals the implication of the circRNA-associated ceRNA network in oesophageal squamous cell carcinoma. Carcinogenesis 2023; 44:596-609. [PMID: 37402652 DOI: 10.1093/carcin/bgad050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 06/05/2023] [Accepted: 07/03/2023] [Indexed: 07/06/2023] Open
Abstract
Circular RNAs (circRNAs) have attracted increasing attention in cancer research. However, there are few studies about the high-throughput sequencing for clinical cohorts focussing on the expression characteristics and regulatory networks of circRNAs in oesophageal squamous cell carcinoma (ESCC) until now. Present study aim to comprehensively recognize the functional and mechanistic patterns of circRNA through constructing a circRNA-related competing endogenous RNA (ceRNA) network in ESCC. Summarily, RNA high-throughput sequencing was adopted to assess the circRNA, miRNA and mRNA expression profiles in ESCC. Through bioinformatics methods, a circRNA-miRNA-mRNA coexpression network was constructed and hub genes was identified. Finally, cellular function experiments combined with bioinformatics analysis were conducted to verify the identified circRNA was involved in the progression of ESCC through ceRNA mechanism. In this study, we established a ceRNA regulatory network, including 5 circRNAs, 7 miRNAs and 197 target mRNAs, and 20 hub genes were screened and identified to exert important roles in the progression of ESCC. As a verification, hsa_circ_0002470 (circIFI6) was revealed to be highly expressed in ESCC and regulate the expression of hub genes by absorbing miR-497-5p and miR-195-5p through ceRNA mechanism. Our results further indicated that silencing of circIFI6 repressed proliferation and migration of ESCC cells, highlighting the tumour promotion effects of circIFI6 in ESCC. Collectively, our study contributes a new insight into the progression of ESCC from the perspective of the circRNA-miRNA-mRNA network, shedding light on the circRNA research in ESCC.
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Affiliation(s)
- Suli Dai
- Research Center, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang 050011, China
- Key Laboratory of Tumor Gene Diagnosis, Prevention and Therapy; Clinical Oncology Research Center, Hebei Province, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Cong Zhang
- Research Center, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang 050011, China
- Key Laboratory of Tumor Gene Diagnosis, Prevention and Therapy; Clinical Oncology Research Center, Hebei Province, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Xiaojian Wei
- Research Center, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang 050011, China
- Key Laboratory of Tumor Gene Diagnosis, Prevention and Therapy; Clinical Oncology Research Center, Hebei Province, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Xiaohan Wang
- Research Center, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang 050011, China
- Key Laboratory of Tumor Gene Diagnosis, Prevention and Therapy; Clinical Oncology Research Center, Hebei Province, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Yang Wen
- Research Center, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang 050011, China
- Key Laboratory of Tumor Gene Diagnosis, Prevention and Therapy; Clinical Oncology Research Center, Hebei Province, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Feng Gao
- Thoracic Surgery Department, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang 050011, China
| | - Lianmei Zhao
- Research Center, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang 050011, China
- Key Laboratory of Tumor Gene Diagnosis, Prevention and Therapy; Clinical Oncology Research Center, Hebei Province, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Baoen Shan
- Research Center, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang 050011, China
- Key Laboratory of Tumor Gene Diagnosis, Prevention and Therapy; Clinical Oncology Research Center, Hebei Province, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
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12
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García-Caballero D, Hart JR, Vogt PK. Long Non-Coding RNAs as "MYC Facilitators". PATHOPHYSIOLOGY 2023; 30:389-399. [PMID: 37755396 PMCID: PMC10534484 DOI: 10.3390/pathophysiology30030030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/15/2023] [Accepted: 08/17/2023] [Indexed: 09/28/2023] Open
Abstract
In this article, we discuss a class of MYC-interacting lncRNAs (long non-coding RNAs) that share the following criteria: They are direct transcriptional targets of MYC. Their expression is coordinated with the expression of MYC. They are required for sustained MYC-driven cell proliferation, and they are not essential for cell survival. We refer to these lncRNAs as "MYC facilitators" and discuss two representative members of this class of lncRNAs, SNHG17 (small nuclear RNA host gene) and LNROP (long non-coding regulator of POU2F2). We also present a general hypothesis on the role of lncRNAs in MYC-mediated transcriptional regulation.
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Affiliation(s)
| | | | - Peter K. Vogt
- Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
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13
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Ying L, Wang J, Feng J, Wu Z. Long non-coding RNA SNHG17 contributes to the progression of pancreatic adenocarcinoma by modulating miR-32-5p/EZH2/STAT3 signaling. Mol Biol Rep 2023:10.1007/s11033-023-08530-1. [PMID: 37253918 DOI: 10.1007/s11033-023-08530-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Accepted: 05/17/2023] [Indexed: 06/01/2023]
Abstract
BACKGROUND Adenocarcinoma of the pancreas (PAAD) is one of the most malignant tumors in the gastrointestinal tract. Long-chain noncoding RNAs (lncRNAs) are non-coding RNAs that are expressed in a variety of cancers. The purpose of this study is to study the expression, biology functions, and molecular mechanism of lncRNA SNHG17 in PAAD. METHODS In this study, qRT-PCR was used to measure the relative expression of SNHG17 and miR-32-5p in PAAD. In order to investigate the effect of SNHG17 and miR-32-5p on the proliferation, migration and invasion of PAAD cells, we performed a variety of tests including CCK-8, colony formation, scratch and transwell assays. Furthermore, SNHG17 and miR-32-5p interactions were confirmed by a luciferase reporter gene test. RESULTS Our results indicate that the expression of SNHG17 in PAAD is elevated, and in vitro studies have shown that SNHG17 enhances the proliferation of PAAD cells, Mechanistically, it has been shown that SNHG17 can direct target miR-32-5p in PAAD cells, thus promoting the proliferation of PAAD cells, migration, and invasion. Furthermore, SNHG17 has been found to activate EZH2/STAT3 signaling pathway through miR-32-5p in PAAD cells. CONCLUSION Our results show that SNHG17 plays a key role in the progression of PAAD by activating STAT3 signaling via regulation of miR-32-5p and EZH2.Identifying these new regulatory pathways may shed light on the underlying mechanism of PAAD and offer a potential therapeutic target for this fatal disease.
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Affiliation(s)
- Liping Ying
- Department of Hepatobiliary Surgery, The Affiliated People's Hospital of Ningbo University, 251 Baizhang East Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
| | - JinBo Wang
- Department of Hepatobiliary Surgery, The Affiliated People's Hospital of Ningbo University, 251 Baizhang East Road, Yinzhou District, Ningbo, 315040, Zhejiang, China.
| | - Jiye Feng
- Department of Hepatobiliary Surgery, The Affiliated People's Hospital of Ningbo University, 251 Baizhang East Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
| | - Zongyang Wu
- Department of Hepatobiliary Surgery, The Affiliated People's Hospital of Ningbo University, 251 Baizhang East Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
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Huang G, Cai G, Hu D, Li J, Xu Q, Chen Z, Xu B. Low SP1 SUMOylation-dependent SNHG17 upregulation promotes drug resistance of gastric cancer through impairing hsa-miR-23b-3p-induced Notch2 inhibition. Cell Oncol (Dordr) 2022; 45:1329-1346. [PMID: 36214997 DOI: 10.1007/s13402-022-00722-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2022] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE Specificity protein 1 (SP1), a transcription factor mediated by SUMOylation modifiers, is upregulated in gastric cancer (GC) and shares negative correlation with patient prognosis. Here, we paid main attention to the role of SP1 SUMOylation in the drug resistance of GC cells and the possible long non-coding RNA (lncRNA) SNHG17/microRNA-23b-3p (miR-23b-3p)/Notch2 network engaged in this process. METHODS Tumor tissues and non-tumor tissues were isolated from GC patients who received treatment with capecitabine and cisplatin (DDP). Co-immunoprecipitation was utilized to detect the SUMOylation level of SP1. Using gain- and loss-of-function approaches, we assessed the impacts of SNHG17/miR-23b-3p/Notch2 on sensitivity of DDP-resistant GC cells in vitro and in vivo. A series of assays such as luciferase activity detection and RNA pull-down were conducted for mechanistic exploration. RESULTS SP1 expression was increased due to low SP1 SUMOylation level in the recurrent GC tissues. This increase led to upregulated SNHG17 expression and SP1 binding sites existed in the SNHG17 promoter. In addition, SNHG17 could bind to miR-23b-3p while miR-23b-3p targeted Notch2. Loss of SNHG17 reduced the resistance of DDP-resistant GC cells to DDP, which was achieved through miR-23b-3p-dependent Notch2 inhibition. Finally, SP1 silencing attenuated the resistance of GC to DDP in mice. CONCLUSION Low SP1 SUMOylation induces SNHG17 upregulation and blocks miR-23b-3p-induced Notch2 inhibition, contributing to the resistance of GC to DDP. This study may aid in the development of therapeutic targets overcoming the chemoresistance of GC.
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Affiliation(s)
- Guoyu Huang
- Department of AnoRectal Surgery, Hainan General Hospital, Hainan, 570105, Haikou, People's Republic of China
| | - Guohao Cai
- Department of AnoRectal Surgery, Hainan General Hospital, Hainan, 570105, Haikou, People's Republic of China
| | - Dongwei Hu
- Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Jinjie Li
- Department of Hepato-pancreato-biliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, South Baixiang Street, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Qigang Xu
- Department of Hepato-pancreato-biliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, South Baixiang Street, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Zongjing Chen
- Department of Hepato-pancreato-biliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, South Baixiang Street, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Bo Xu
- Department of Hepato-pancreato-biliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, South Baixiang Street, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China.
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Huang T, Wu Z, Zhu S. The roles and mechanisms of the lncRNA-miRNA axis in the progression of esophageal cancer: a narrative review. J Thorac Dis 2022; 14:4545-4559. [PMID: 36524088 PMCID: PMC9745524 DOI: 10.21037/jtd-22-1449] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 11/08/2022] [Indexed: 12/08/2023]
Abstract
BACKGROUND AND OBJECTIVE Esophageal cancer is one of the most common malignant digestive tract tumors. Despite various treatment methods, the prognosis of patients remains unsatisfactory, largely due to an insufficient understanding of the mechanisms involved in the pathogenesis and progression of esophageal cancer. More than 98% of the nucleotide sequences in the human genome do not encode proteins, and their transcription products are noncoding RNAs (ncRNAs), mainly long noncoding RNAs (lncRNAs) and microRNAs (miRNAs). Experiments have shown that lncRNAs and miRNAs play crucial roles in the occurrence and progression of various human malignancies. These ncRNAs influence the progression of esophageal cancer through an intricate regulatory network. We herein summarized the roles and mechanisms of the lncRNA-miRNA axis in esophageal cancer cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), invasion and metastasis, drug resistance, radiotherapy resistance, and angiogenesis. This review provides a rationale for anticancer therapy that targets the lncRNA-miRNA axis in esophageal cancer. METHODS Related articles published in the PubMed database between 05/30/2008 to 09/10/2022 were identified using the following terms: "lncRNA AND miRNA AND esophageal cancer", "lncRNA AND miRNA AND cell proliferation", "lncRNA AND miRNA AND apoptosis", "lncRNA AND miRNA AND EMT", "lncRNA AND miRNA AND invasion and metastasis", "lncRNA AND miRNA AND drug resistance", and "lncRNA AND miRNA AND radiotherapy resistance". Published articles written in English available to readers were considered. KEY CONTENT AND FINDINGS We summarized the roles of the lncRNA-miRNA axis in the progression of esophageal cancer, including cell proliferation, apoptosis, EMT, invasion and metastasis, drug resistance, radio resistance, and other progressions, and determined that the lncRNA-miRNA axis may serve as a potential clinical treatment target for esophageal cancer. CONCLUSIONS The lncRNA-miRNA axis is closely related to the progression of esophageal cancer and may act as a potential biological target for the clinical treatment of patients with esophageal cancer.
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Affiliation(s)
- Tao Huang
- Department of Thoracic Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, China
- Research Laboratory of Tumor Microenvironment, Wannan Medical College, Wuhu, China
| | - Zhihao Wu
- Research Laboratory of Tumor Microenvironment, Wannan Medical College, Wuhu, China
- School of Preclinical Medicine, Wannan Medical College, Wuhu, China
| | - Shaojin Zhu
- Department of Thoracic Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, China
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Zhang G, Fu L, Wang Y, Liu B, Ma S, Ma H, Zhang H, Zhang F, Yang K, Cai H. Integrative pan-cancer analysis indicates the prognostic importance of long noncoding RNA SNHG17 in human cancers. Pathol Res Pract 2022; 238:154140. [PMID: 36167008 DOI: 10.1016/j.prp.2022.154140] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/18/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Cancer is one of the most widespread causes of death today. Early diagnosis can dramatically reduce cancer-related mortality. Studies have shown that the lncRNA Small Nucleolar RNA Host Gene 17 (SNHG17) is aberrantly expressed in various types of solid tumors. Nevertheless, its prognostic value remains to be elucidated. The main objective of this meta-analysis was to elucidate whether SNHG17 can be considered as a potential prognostic biomarker for a variety of cancers. METHODS Correlational studies were screened from Cochrane, Embase, PubMed, and Web of Science. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled, and the role of SNHG17 in cancer was analyzed. The Cancer Genome Atlas (TCGA) database was employed to verify the results. RESULTS Seventeen original papers including 1451 patients were included in the meta-analysis. SNHG17 expression was upregulated in various cancers. Overexpression of SNHG17 was significantly correlated with worse overall survival (OS) (HR = 1.92, 95% CI 1.55-2.37, P < 0.001) and relapse-free survival (RFS) (HR = 1.87, 95% CI 1.06-3.30, P = 0.030). Furthermore, overexpression of SNHG17 was predictive of earlier lymph node metastasis (LNM) (OR = 2.94, 95% CI 2.29-3.78, P < 0.001), more advanced tumor-node-metastases (TNM) stage (OR = 3.56, 95% CI 2.22-5.68, P < 0.001), larger tumor size (OR = 2.18, 95% CI 1.65-2.88, P < 0.001), worse differentiation grade (OR = 1.69, 95% CI 1.26-2.25, P < 0.001), and earlier distant metastasis (DM) (OR = 1.63, 95% CI 1.03-2.56, P = 0.033) in human cancers. Moreover, further inquiry based on TCGA dataset validated that SNHG17 was high expression in various tumors and foresaw unfavorable clinical prognosis. CONCLUSIONS Overexpression of SNHG17 correlates with poor prognosis and advanced clinicopathological features in cancer patients and may be a potential prognostic indicator and a therapeutic target for cancer treatment.
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Affiliation(s)
- Guangming Zhang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730000, China; Gansu Provincial Hospital, Lanzhou 730000, China
| | - Liangyin Fu
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730000, China; Gansu Provincial Hospital, Lanzhou 730000, China
| | | | - Bin Liu
- Gansu Provincial Hospital, Lanzhou 730000, China
| | - Shixun Ma
- Gansu Provincial Hospital, Lanzhou 730000, China
| | - Haizhong Ma
- Gansu Provincial Hospital, Lanzhou 730000, China
| | - Helin Zhang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China
| | - Fan Zhang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China
| | - Kehu Yang
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Hui Cai
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730000, China; Gansu Provincial Hospital, Lanzhou 730000, China; NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou 730000, China.
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Zhang N, Sun Y, Wang T, Xu X, Cao M. Enabling factor for cancer hallmark acquisition: Small nucleolar RNA host gene 17. Front Oncol 2022; 12:974939. [PMID: 36185210 PMCID: PMC9515549 DOI: 10.3389/fonc.2022.974939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/19/2022] [Indexed: 11/25/2022] Open
Abstract
The role of long non-coding RNA (lncRNA) in human tumors has gradually received increasing attention in recent years. Particularly, the different functions of lncRNAs in different subcellular localizations have been widely investigated. The upregulation of lncRNA small nucleolar RNA host gene 17 (SNHG17) has been observed in various human tumors. Growing evidence has proved that SNHG17 plays a tumor-promoting role in tumorigenesis and development. This paper describes the molecular mechanisms by which SNHG17 contributes to tumor formation and development. The different functions of SNHG17 in various subcellular localizations are also emphasized: its function in the cytoplasm as a competing endogenous RNA (ceRNA), its action in the nucleus as a transcriptional coactivator, and its function through the polycomb repressive complex 2 (PRC2)-dependent epigenetic modifications that regulate transcriptional processes. Finally, the correlation between SNHG17 and human tumors is summarized. Its potential as a novel prognostic and diagnostic biomarker for cancer is explored especially.
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Affiliation(s)
- Ningzhi Zhang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yuanyuan Sun
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Tuo Wang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xinyuan Xu
- Medical Affairs Department, Harbin Medical University Cancer Hospital, Harbin, China
| | - Mengru Cao
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
- *Correspondence: Mengru Cao,
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18
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CKAP2L Promotes Esophageal Squamous Cell Carcinoma Progression and Drug-Resistance by Modulating Cell Cycle. JOURNAL OF ONCOLOGY 2022; 2022:2378253. [PMID: 36090903 PMCID: PMC9462994 DOI: 10.1155/2022/2378253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 05/19/2022] [Accepted: 07/12/2022] [Indexed: 12/24/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer and the leading cause of cancer-related mortality worldwide, especially in Asia. In this study, the gene CKAP2L was selected by GEO, TCGA, and GTEx database analysis. The high expression of CKAP2L is related to the occurrence and development of ESCC. In addition, CKAP2L knockdown can inhibit the growth and migration of ESCC cells, while CKAP2L overexpression has the opposite effect. Furthermore, in vivo experiments indicated that down-regulation of CKAP2L can inhibit the tumorigenesis of ESCC cells. KEGG pathway analysis and the STRING database explored the relationship between cell cycle and CKAP2L and verified that depletion of CKAP2L markedly arrested cell cycle in the G2/M phase. Meanwhile, CKAP2L knockdown increased the sensitivity of ESCC cells to flavopiridol, the first CDK inhibitor to be tested in clinical trials, leading to an observable reduction in cell proliferation and an increase in cellular apoptosis. In brief, we identified CKAP2L as a tumor promoter, potential prognostic indicator, and therapeutic target of ESCC, which may play a role in regulating cell cycle progression.
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Su M, Tang J, Yang D, Wu Z, Liao Q, Wang H, Xiao Y, Wang W. Oncogenic roles of the lncRNA LINC00460 in human cancers. Cancer Cell Int 2022; 22:240. [PMID: 35906593 PMCID: PMC9336008 DOI: 10.1186/s12935-022-02655-2] [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: 12/22/2021] [Accepted: 07/17/2022] [Indexed: 11/24/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) represent an important group of endogenous RNAs with limit protein-encoding capability, with a length of more than 200 nucleotides. Emerging evidence have demonstrated that lncRNAs are greatly involved in multiple cancers by playing critical roles in tumor initiation and progression. Long intergenic non-protein coding RNA 460 (LINC00460), a novel cancer-related lncRNA, exhibits abnormal expression and oncogenic function in multiple cancers, and positively correlates with poor clinical characteristics of cancer patients. LINC00460 has also been shown to be a promising biomarker for diagnosis as well as prognostic evaluation in cancer patients. In this review, we briefly summarized recent knowledge on the expression, functional roles, molecular mechanisms, and diagnostic and prognostic values of LINC00460 in human malignancies.
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Affiliation(s)
- Min Su
- Thoracic Surgery Department 2, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China.,Hunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal Carcinoma, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China.,Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, People's Republic of China.,Hunan Key Laboratory of Translational Radiation Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Hunan, 410013, Changsha, People's Republic of China
| | - Jinming Tang
- Thoracic Surgery Department 2, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China.,Hunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal Carcinoma, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China
| | - Desong Yang
- Thoracic Surgery Department 2, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China.,Hunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal Carcinoma, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China
| | - Zhining Wu
- Thoracic Surgery Department 2, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China.,Hunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal Carcinoma, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China
| | - Qianjin Liao
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, People's Republic of China
| | - Hui Wang
- Hunan Key Laboratory of Translational Radiation Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Hunan, 410013, Changsha, People's Republic of China
| | - Yuhang Xiao
- Hunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal Carcinoma, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China. .,Department of Pharmacy, Xiangya Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410001, People's Republic of China.
| | - Wenxiang Wang
- Thoracic Surgery Department 2, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China. .,Hunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal Carcinoma, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China.
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Ma L, Gao J, Zhang N, Wang J, Xu T, Lei T, Zou X, Wei C, Wang Z. Long noncoding RNA SNHG17: a novel molecule in human cancers. Cancer Cell Int 2022; 22:104. [PMID: 35248073 PMCID: PMC8897953 DOI: 10.1186/s12935-022-02529-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 02/21/2022] [Indexed: 01/13/2023] Open
Abstract
AbstractMany studies in recent years have found that dysregulation of long non-coding RNAs (lncRNAs) can contribute to disease. Small nucleolar RNA host gene 17 (SNHG17) is a novel cancer-related lncRNA of the SNHG family which is highly expressed in various tumors and may exert oncogenic functions. Several studies have demonstrated that SNHG17 is closely related to the proliferation, migration, invasion, apoptosis, and chemical drug resistance of tumor cells, and clinical studies have found an association between high SNHG17 expression and poor prognosis. In this review, we summarize relevant studies investigating SNHG17, focusing on its biological function as well as its potential value for clinical applications.
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Guo Y, Sun P, Guo W, Yin Q, Han J, Sheng S, Liang J, Dong Z. LncRNA DDX11 antisense RNA 1 promotes EMT process of esophageal squamous cell carcinoma by sponging miR-30d-5p to regulate SNAI1/ZEB2 expression and Wnt/β-catenin pathway. Bioengineered 2021; 12:11425-11440. [PMID: 34866524 PMCID: PMC8810181 DOI: 10.1080/21655979.2021.2008759] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 11/05/2021] [Accepted: 11/05/2021] [Indexed: 12/11/2022] Open
Abstract
LncRNA DDX11 antisense RNA 1 (DDX11-AS1) is recognized as having an imperative oncogenic role in different types of human cancer. Nevertheless, the functions, as well as the basic mechanisms of DDX11-AS1 in the EMT process of esophageal squamous cell carcinoma (ESCC), are yet to be clarified. In this research, high DDX11-AS1 expression was detected in ESCC cells as well as tissues and was linked to the poor prognosis of patients with ESCC. DDX11-AS1 promoted cell proliferation, migration, invasion ability and epithelial mesenchymal transition (EMT) process in vitro. Mechanistic analysis depicted that DDX11-AS1 may function as a ceRNA through sponging miR-30d-5p to upregulate the expression of SNAI1 and ZEB2. Meanwhile, overexpression of DDX11-AS1 might cause the activation of the Wnt/β-catenin signaling pathway via targeting miR-30d-5p. On the whole, the findings of this research illustrate that DDX11-AS1 may act as an EMT-related lncRNA to advance ESCC progression through sponging miR-30d-5p to regulate SNAI1/ZEB2 expression and activate the Wnt/β-catenin pathway, which indicates that it might serve as a probable therapeutic target for ESCC.
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Affiliation(s)
- Yanli Guo
- Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Pingping Sun
- Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Wei Guo
- Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Qing Yin
- Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Junshu Han
- Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Supeng Sheng
- Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jia Liang
- Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhiming Dong
- Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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