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Elimam H, Moussa R, Radwan AF, Hatawsh A, Elfar N, Alhamshry NAA, Abd-Elmawla MA, Aborehab NM, Zaki MB, Mageed SSA, Mohammed OA, Abdel-Reheim MA, Doghish AS. LncRNAs orchestration of gastric cancer - particular emphasis on the etiology, diagnosis, and treatment resistance. Funct Integr Genomics 2024; 24:175. [PMID: 39325107 DOI: 10.1007/s10142-024-01450-8] [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: 08/23/2024] [Revised: 09/05/2024] [Accepted: 09/07/2024] [Indexed: 09/27/2024]
Abstract
Gastric cancer (GC) remains a major public health challenge worldwide. Long non-coding RNAs (lncRNAs) play important roles in the development, progression, and resistance to the treatment of GC, as shown by recent developments in molecular characterization. Still, an in-depth investigation of the lncRNA landscape in GC is absent. However, The objective of this systematic review is to evaluate our present understanding of the role that lncRNA dysregulation plays in the etiology of GC and treatment resistance, with a focus on the underlying mechanisms and clinical implications. Research that described the functions of lncRNA in angiogenesis, stemness, epigenetics, metastasis, apoptosis, development, and resistance to key treatments was given priority. In GC, it has been discovered that a large number of lncRNAs, including MALAT1, HOTAIR, H19, and ANRIL, are aberrantly expressed and are connected with disease-related outcomes. Through various methods such as chromatin remodeling, signal transduction pathways, and microRNA sponging, they modulate hallmark cancer capabilities. Through the activation of stemness programs, epithelial-mesenchymal transition (EMT), and survival signaling, LncRNAs also control resistance to immunotherapy, chemotherapy, and targeted therapies. By clarifying their molecular roles further, we may be able to identify new treatment targets and ways to overcome resistance. This article aims to explore the interplay between lncRNAs, and GC. Specifically, the focus is on understanding how lncRNAs contribute to the etiology of GC and influence treatment resistance in patients with this disease.
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Affiliation(s)
- Hanan Elimam
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt
| | - Rewan Moussa
- Faculty of Medicine, Helwan University, Cairo, 11795, Egypt
| | - Abdullah F Radwan
- Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo, 11829, Egypt
| | - Abdulrahman Hatawsh
- Biotechnology School, 26th of July Corridor, Nile University, Sheikh Zayed City, Giza, 12588, Egypt
| | - Nourhan Elfar
- School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Cairo, 11578, Egypt
- Egyptian Drug Authority (EDA), Ministry of Health and Population, Cairo, 11567, Egypt
| | - Nora A A Alhamshry
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt
| | - Mai A Abd-Elmawla
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Nora M Aborehab
- Member of Institutional Animal Care and Use Committee (IACUC), Cairo University, Cairo, Egypt
| | - Mohamed Bakr Zaki
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia
| | | | - Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt.
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Oh JH, Kim CY, Jeong DS, Kim YC, Kim MH, Cho JY. The homeoprotein HOXB2 limits triple-negative breast carcinogenesis via extracellular matrix remodeling. Int J Biol Sci 2024; 20:1045-1063. [PMID: 38322121 PMCID: PMC10845296 DOI: 10.7150/ijbs.88837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 12/31/2023] [Indexed: 02/08/2024] Open
Abstract
Homeobox genes and their encoded DNA-binding homeoproteins are master regulators of development. Consequently, these homeotic elements may regulate key steps in cancer pathogenesis. Here, using a combination of in silico analyses of large-scale patient datasets, in vitro RNAi phenotyping, and in vivo validation studies, we investigated the role of HOXB2 in different molecular subtypes of human breast cancer (BC). The gene expression signatures of HOXB2 are different across distinct BC subtypes due to various genetic alterations, but HOXB2 was specifically downregulated in the aggressive triple-negative subtype (TNBC). We found that the reduced expression of HOXB2 was correlated with the metastatic abilities (epithelial-to-mesenchymal transition) of TNBC cells. Further, we revealed that HOXB2 restrained TNBC aggressiveness by ECM organization. HOXB2 bound to the promoter regions of MATN3 and ECM2 and regulated their transcription levels. Forced expression of HOXB2 effectively prevented TNBC progression and metastasis in a mouse xenograft model. Reduction of HOXB2 and the HOXB2/MATN3/ECM2 transcriptional axis correlated with poor survival in patients with various cancers. Further, we found the long non-coding RNA HOXB-AS1 in complex with SMYD3, a lysine methyltransferase, as an epigenetic switch controlling HOXB2 expression. Overall, our results indicate a tumor-suppressive role of HOXB2 by maintaining ECM organization and delineate potential clinical utility of HOXB2 as a marker for TNBC patients.
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Affiliation(s)
- Ji Hoon Oh
- Department of Biological Sciences, Keimyung University College of Natural Sciences, Daegu, Republic of Korea
| | - Clara Yuri Kim
- Department of Anatomy, Embryology Laboratory, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Da Som Jeong
- Department of Anatomy, Embryology Laboratory, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yu Cheon Kim
- Department of Anatomy, Embryology Laboratory, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myoung Hee Kim
- Department of Anatomy, Embryology Laboratory, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Je-Yoel Cho
- Department of Biochemistry, Brain Korea 21 Project and Research Institute for Veterinary Science, Seoul National University College of Veterinary Medicine, Seoul, Republic of Korea
- Comparative Medicine Disease Research Center, Seoul National University, Seoul, Republic of Korea
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Li Z, Lang Z, Wang T, Qu G, Sui W, Liu J. LncRNA SNHG22 promotes gastric cancer progression by regulating the miR-101-3p/e2f2 axis. Cell Cycle 2023; 22:347-360. [PMID: 36281526 PMCID: PMC9851253 DOI: 10.1080/15384101.2022.2119515] [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: 06/27/2021] [Revised: 04/04/2022] [Accepted: 08/26/2022] [Indexed: 01/22/2023] Open
Abstract
Gastric cancer (GC) still poses a significant threat to human life. Hence, there is an urgent need to understand the mechanism of GC progression and develop novel therapeutics approach to treating GC. This study was conducted to evaluate the role of the lncRNA SNHG22 in the progression of GC. First, GC data from TCGA were analyzed using GEPIA. After the starbase database was used to predict SNHG22 target miRNA and miR-101-3p target mRNA. The predictions were validated using a dual-luciferase reporter assay, biotinylated RNA pull-down assay, and RIP-qRT-PCR. The relative expression of SNHG22, miR-101-3p, and E2F2 was measured by qRT-PCR and western blot (WB) analysis, while the mechanism of GC cell proliferation was elucidated through the colony formation and CCK-8 assay. Our result showed that SNHG22 was upregulated significantly in GC tissue samples from TCGA database, GC cell lines, and clinical tissue samples, and its expression was related to low survival rate of gastric cancer patients. Bioinformatics prediction predicted miR-101-3p as the potential target of SNHG22 and E2F2 genes as miR-101-3p target mRNA. We found that E2F2 expression was negatively associated with overall survival of GC patients. Functional study showed that silencing SNHG22 markedly inhibited the proliferation, migration, and invasion of GC cells as well as in vivo tumor growth. This was reversed after inhibiting miR-101-3p or overexpressing E2F2. The lncRNA SNHG22 promotes the proliferation, migration, and invasion of GC cells via the miR-101-3p/E2F2 axis. SNHG22 might be a potential prognostic indicator in gastric cancer.
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Affiliation(s)
- Zhen Li
- Department of General & Pediatric surgery, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China
| | - Zhiqiang Lang
- Department of Pathology, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China
| | - Ting Wang
- Department of Pathology, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China
| | - Guimei Qu
- Department of Pathology, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China
| | - Wu Sui
- Department of General & Pediatric surgery, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China
| | - Jing Liu
- Department of Pathology, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China
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Raval M, Mishra S, Tiwari AK. Epigenetic regulons in Alzheimer's disease. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2023; 198:185-247. [DOI: 10.1016/bs.pmbts.2023.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/31/2023]
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Yuan W, Huang J, Hou S, Li H, Bie L, Chen B, Li G, Zhou Y, Chen X. The Antigastric Cancer Effect of Triptolide is Associated With H19/NF-κB/FLIP Axis. Front Pharmacol 2022; 13:918588. [PMID: 36110523 PMCID: PMC9469193 DOI: 10.3389/fphar.2022.918588] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 06/02/2022] [Indexed: 12/11/2022] Open
Abstract
Background and Objective: Triptolide (TP), one of the fat-soluble components extracted from the Chinese medicinal herb Tripterygium wilfordii Hook F. (TWHF), possesses strong antitumor bioactivities, but its dose-dependent side effects restrict its wide application. This study was designed to investigate whether inflammatory factors increased the antitumor effects of the nontoxic dose of TP on gastric cancer cells and tried to explore the possible molecular mechanisms. Method: AGS and MKN45 cells were treated with different doses of TP and TNF-α. Cell viability and apoptosis were detected in vitro. In addition, NF-κB mediated prosurvival signals and cytoprotective proteins, especially FLICE-inhibitory protein (FLIP), were detected to determine their effects on TP/TNF-α–induced apoptosis. Moreover, the function of lncRNA H19/miR-204-5p/NF-κB/FLIP axis was investigated in vitro, and the antigastric cancer effect of TP plus TNF-α was proved in the mice xenograft model. Result:In vitro experimental results showed that TP pretreatment promoted apoptosis in AGS and MKN45 cells upon TNF-α exposure. TP/TNF-α–mediated apoptosis was partly mediated by the inhibitory effect of NF-κB–mediated FLIP expression. Oncogene H19 lying in the upstream pathway of NF-κB played a vital role upon TNF-α exposure, and bioinformatics analysis proved that H19 participated in TP/TNF-α–induced apoptosis via binding of miR-204-5p. Lastly, a low dose of TP and TNF-α inhibited the tumor weight and tumor volume of AGS and MKN45 cells in vivo. Conclusion: TP pretreatment increased apoptosis in TNF-α–stimulated gastric cancer cells, which are dependent on the disruption of the H19/miR-204-5p/NF-κB/FLIP axis. Cotreatment of TP and TNF-α is a better option for enhancing the anticancer effect and lowering the side effect of TP.
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Affiliation(s)
- Weiwei Yuan
- Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Jinxi Huang
- Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Shanshan Hou
- Department of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, China
| | - Huahua Li
- Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Liangyu Bie
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou University, Zhengzhou, China
| | - Beibei Chen
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou University, Zhengzhou, China
| | - Gaofeng Li
- Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Yang Zhou
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou University, Zhengzhou, China
- *Correspondence: Xiaobing Chen, ; Yang Zhou,
| | - Xiaobing Chen
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou University, Zhengzhou, China
- *Correspondence: Xiaobing Chen, ; Yang Zhou,
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Gao SS, Zhang ZK, Wang XB, Ma Y, Yin GQ, Guo XB. Role of transcribed ultraconserved regions in gastric cancer and therapeutic perspectives. World J Gastroenterol 2022; 28:2900-2909. [PMID: 35978878 PMCID: PMC9280734 DOI: 10.3748/wjg.v28.i25.2900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 04/08/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is the fourth leading cause of cancer-related death. The occurrence and development of GC is a complex process involving multiple biological mechanisms. Although traditional regulation modulates molecular functions related to the occurrence and development of GC, the comprehensive mechanisms remain unclear. Ultraconserved region (UCR) refers to a genome sequence that is completely conserved in the homologous regions of the human, rat and mouse genomes, with 100% identity, without any insertions or deletions, and often located in fragile sites and tumour-related genes. The transcribed UCR (T-UCR) is transcribed from the UCR and is a new type of long noncoding RNA. Recent studies have found that the expression level of T-UCRs changes during the occurrence and development of GC, revealing a new mechanism underlying GC. Therefore, this article aims to review the relevant research on T-UCRs in GC, as well as the function of T-UCRs and their regulatory role in the occurrence and development of GC, to provide new strategies for GC diagnosis and treatment.
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Affiliation(s)
- Shen-Shuo Gao
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Zhi-Kai Zhang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Xu-Bin Wang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Yan Ma
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Guo-Qing Yin
- Department of Anus and Intestine Surgery, Qingzhou Hospital Affiliated to Shandong First Medical University, Qingzhou 262500, Shandong Province, China
| | - Xiao-Bo Guo
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
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The Targeting of Noncoding RNAs by Quercetin in Cancer Prevention and Therapy. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:4330681. [PMID: 35656022 PMCID: PMC9155922 DOI: 10.1155/2022/4330681] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 05/11/2022] [Indexed: 12/14/2022]
Abstract
The dietary flavonoid quercetin is ubiquitously distributed in fruits, vegetables, and medicinal herbs. Quercetin has been a focal point in recent years due to its versatile health-promoting benefits and high pharmacological values. It has well documented that quercetin exerts anticancer actions by inhibiting cell proliferation, inducing apoptosis, and retarding the invasion and metastasis of cancer cells. However, the exact mechanism of quercetin-mediated cancer chemoprevention is still not fully understood. With the advances in high-throughput sequencing technologies, the intricate oncogenic signaling networks have been gradually characterized. Increasing evidence on the close association between noncoding RNA (ncRNAs) and cancer etiopathogenesis emphasizes the potential of ncRNAs as promising molecular targets for cancer treatment. Available experimental studies indicate that quercetin can dominate multiple cancer-associated ncRNAs, hence repressing carcinogenesis and cancer development. Thus, modulation of ncRNAs serves as a key mechanism responsible for the anticancer effects of quercetin. In this review, we focus on the chemopreventive effects of quercetin on cancer pathogenesis by targeting cancer-relevant ncRNAs, supporting the viewpoint that quercetin holds promise as a drug candidate for cancer chemoprevention and chemotherapy. An in-depth comprehension of the interplay between quercetin and ncRNAs in the inhibition of cancer development and progression will raise the possibility of developing this bioactive compound as an anticancer agent that could be highly efficacious and safe in clinical practice.
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Shan KS, Li WW, Ren W, Kong S, Peng LP, Zhuo HQ, Tian SB. LncRNA cancer susceptibility 20 regulates the metastasis of human gastric cancer cells via the miR-143-5p/MEMO1 molecular axis. World J Gastroenterol 2022; 28:1656-1670. [PMID: 35581960 PMCID: PMC9048782 DOI: 10.3748/wjg.v28.i16.1656] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 12/26/2021] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is considered as one of the most widespread malignancies. Emerging evidence has shown that lncRNAs can function as important oncogenes or tumor suppressors during GC progression.
AIM To investigate the effect and mechanism of lncRNA cancer susceptibility 20 (CASC20) in the proliferation and metastasis of GC cells.
METHODS Data mining and clinical samples were used to evaluate the expression of CASC20 in GC and adjacent tissues. CASC20 was down-regulated in GC cells by short-interfering RNA. Cell proliferation was evaluated by CCK-8 assay, and cell migration and invasion were detected by wound healing and Transwell assays. The expressions of proteins related to epithelial-mesenchymal transition were detected by western blot assay.
RESULTS The expression of CASC20 was increased in GC tumor tissues and various GC cell lines. High CASC20 expression was correlated with a high risk of lymphatic metastasis and poor prognosis in GC patients. In vitro assays showed that silencing CASC20 reduced cell proliferation, migration, and invasion in GC cells. Mechanistic studies revealed that CASC20 exhibits oncogenic functions by regulating MEMO1 expression through competitive endogenous binding to miR-143-5p, leading to induction of epithelial-mesenchymal transition.
CONCLUSION Our findings indicate that CASC20 serves as a tumor promoter by regulating metastasis in GC via the miR-143-5p/MEMO1 axis. CASC20 may be a potential therapeutic target for GC.
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Affiliation(s)
- Ke-Shu Shan
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Wei-Wei Li
- Department of Critical Care Medicine, The 960th Hospital of the People's Liberation Army Joint Logistics Support Force, Jinan 250031, Shandong Province, China
| | - Wang Ren
- Department of General Surgery, People's Hospital of Sishui County, Jining 273200, Shandong Province, China
| | - Shuai Kong
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Li-Pan Peng
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Hong-Qing Zhuo
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Shu-Bo Tian
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
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LncRNA HOTAIR promotes proliferation and suppresses apoptosis of mouse spermatogonium GC-1 cells by sponging miR-761 to modulate NANOS2 expression. In Vitro Cell Dev Biol Anim 2022; 58:295-306. [PMID: 35426065 DOI: 10.1007/s11626-022-00657-y] [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: 10/22/2021] [Accepted: 02/06/2022] [Indexed: 12/12/2022]
Abstract
LncRNA HOX antisense intergenic RNA (HOTAIR) can regulate cancer-related gene expression and promote stem cell and tumor cell proliferation via mechanisms including the competing endogenous RNA (ceRNA) mechanism. HOTAIR is abundantly expressed in the genital tubercle of E11.5, E12.5, and E13.5 embryos, whereas it became barely detectable at E13.5 and expressed again in adult mouse testis. However, the underlying function and mechanism of HOTAIR in spermatogenesis have not been elucidated. Interestingly, other researchers reported that the function of gene Nanos C2HC-Type Zinc Finger 2 (nanos2) includes the maintenance of both the primordial germ cells (PGCs) and germline stem cells, and Nanos2 protein and transcripts (NANOS2) were detected only in PGCs from day E11.5 and undifferentiated spermatogonia in spermatogenesis. We therefore investigated the relationship between HOTAIR and NANOS2 in maintaining spermatogonial stem cell population. We found that, compared to the adult mouse, the expression levels of HOTAIR and NANOS2 in embryo mouse were significantly higher and miR-761expression level was lower. In mouse GC-1 spermatogonia cells, overexpression of miRNA-761 significantly inhibited the expression of NANOS2 and HOTAIR, suppressed the proliferation, and promotes apoptosis of cells. Knock down and overexpression of HOTAIR indicated that HOTAIR expression was positively correlated with NANOS2 expression; overexpressed HOTAIR could promote proliferation and suppresses apoptosis of GC-1 cells. By a rescue experiment and dual luciferase reporter assay, miR-761 was identified as a direct target of HOTAIR, and NANOS2 was identified as the direct target of miR-761. The above results indicate that HOTAIR promotes proliferation and suppresses apoptosis of mouse spermatogonium GC-1 cells by sponging miR-761 to modulate NANOS2 expression. Our findings elucidate one of possible mechanisms and importance of HOTAIR in maintaining spermatogonial stem cell population, and provide new candidate genes and possible pathogenesis for male infertility.
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Xu J, Liu XY, Zhang Q, Liu H, Zhang P, Tian ZB, Zhang CP, Li XY. Crosstalk Among YAP, LncRNA, and Tumor-Associated Macrophages in Tumorigenesis Development. Front Oncol 2022; 11:810893. [PMID: 35071016 PMCID: PMC8770286 DOI: 10.3389/fonc.2021.810893] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 12/13/2021] [Indexed: 12/14/2022] Open
Abstract
Long non-coding RNAs (ncRNAs), which do not encode proteins, regulate cell proliferation, tumor angiogenesis, and metastasis and are closely associated with the development, progression, and metastasis of many cancers. Tumor-associated macrophages (TAMs) in the tumor microenvironment play an important role in cancer progression. The Hippo signaling pathway regulates cell proliferation and apoptosis, maintains tissue and organ size, and homeostasis of the internal environment of organisms. Abnormal expression of Yes-associated protein (YAP), the Hippo signaling pathway key component, is widely observed in various malignancies. Further, TAM, lncRNA, and YAP are currently valuable targets for cancer immunotherapy. In this review, we have logically summarized recent studies, clarified the close association between the three factors and tumorigenesis, and analyzed the outlook of tumor immunotherapy.
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Affiliation(s)
- Jing Xu
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Innovation Platform of Marine Drug Screening & Evaluation, Qingdao Pilot National Laboratory for Marine Science and Technology, Qingdao, China
| | - Xin-Yuan Liu
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Qi Zhang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hua Liu
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Peng Zhang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zi-Bin Tian
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Cui-Ping Zhang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiao-Yu Li
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
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Tayefeh-Gholami S, Ghanbari M, Aghazadeh A, Rajabi A, Saber A, Hussen BM, Farsad-Akhtar N, Safaralizadeh R. Prognostic Value of LncRNA KRT18P55 in Patients with Intestinal Type of Gastric Cancer. J Gastrointest Cancer 2021; 53:1014-1019. [PMID: 34766250 DOI: 10.1007/s12029-021-00744-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/22/2021] [Indexed: 12/25/2022]
Abstract
PURPOSE Gastric cancer (GC) is a heterogeneous disease, and this heterogeneity significantly affects survival and treatment outcomes. Identification of molecular biomarkers specific for early-stage GC can help clinicians to choose more precise and effective treatment approaches. Long non-coding RNAs (lncRNAs) have the potential to be used as biomarkers because of their tissue specificity, stability, and availability in body fluids. In this study, we aimed to investigate changes in the expression levels of lncRNA KRT18P55 and to assess its biomarker potentials in patients with GC. METHODS Tumor and non-tumor marginal tissues were collected from 102 patients at Noor-Nejat Hospital (Tabriz, Iran). RNA was isolated, and quantitative reverse transcriptase PCR (qRT-PCR) was performed to assess KRT18P55 expression levels in tumor and non-tumor tissue samples. The receiver operating characteristic (ROC) curve analysis was performed to evaluate potentials of KRT18P55 as a prognostic biomarker in GC. SPSS and GraphPad Prism software were used for data analysis. RESULTS We found that KRT18P55 is significantly overexpressed in tumor as compared to non-tumor tissues (p < 0.0001). We found a significant association between KRT18P55 overexpression and intestinal GC subtype (p < 0.0001), lymph node metastasis (p = 0.013), and Helicobacter pylori infection (p = 0.033). Based on the ROC analysis, KRT18P55 showed a sensitivity and specificity of 53.92% and 77.45%, respectively. CONCLUSION Overexpression of KRT18P55 in gastric tumors is suggestive of its oncogenic role in GC. In addition, KRT18P55 may be used as a potential prognosis biomarker and therapeutic target in intestinal GC subtype.
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Affiliation(s)
- Samaneh Tayefeh-Gholami
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Mohammad Ghanbari
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Aida Aghazadeh
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Ali Rajabi
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Ali Saber
- Zimagene Medical Genetics Laboratory, Avicenna St, Hamedan, Iran
| | - Bashdar Mahmud Hussen
- Department of Pharmacognocy, College of Pharmacy, Hawler Medical University, Erbil, Iraq
| | - Nader Farsad-Akhtar
- Department of Plant Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Reza Safaralizadeh
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
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12
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Gui Z, Zhao Z, Sun Q, Shao G, Huang J, Zhao W, Kuang Y. LncRNA FEZF1-AS1 Promotes Multi-Drug Resistance of Gastric Cancer Cells via Upregulating ATG5. Front Cell Dev Biol 2021; 9:749129. [PMID: 34790665 PMCID: PMC8591218 DOI: 10.3389/fcell.2021.749129] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 10/04/2021] [Indexed: 12/19/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) play important roles in human cancers including gastric cancer (GC). Dysregulation of lncRNAs is involved in a variety of pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of FEZF1-AS1 in chemoresistance of GC remain unknown. In this study, we aimed to determine the role of FEZF1-AS1 in chemoresistance of GC. The level of FEZF1-AS1 in GC tissues and GC cell lines was assessed by qRT-PCR. Our results showed that the expression of FEZF1-AS1 was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identified that high level of FEZF1-AS1 is an independent predictor for poor overall survival. Increased FEZF1-AS1 expression promoted gastric cancer cell proliferation in vitro. Additionally, FEZF1-AS1 was upregulated in chemo-resistant GC tissues. The regulatory effect of FEZF1-AS1 on multi-drug resistance (MDR) in GC cells and the underlying mechanism was investigated. It was found that increased FEZF1-AS1 expression promoted chemo-resistance of GC cells. Molecular interactions were determined by RNA immunoprecipitation (RIP) and the results showed that FEZF1-AS1 regulated chemo-resistance of GC cells through modulating autophagy by directly targeting ATG5. The proliferation and autophagy of GC cells promoted by overexpression of LncFEZF1-AS1 was suppressed when ATG5 was knocked down. Moreover, knockdown of FEZF1-AS1 inhibited tumor growth and increased 5-FU sensitivity in GC cells in vivo. Taken together, this study revealed that the FEZF1-AS1/ATG5 axis regulates MDR of GC cells via modulating autophagy.
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Affiliation(s)
- Zhifu Gui
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- Department of General Surgery, Jiangyin Hospital Affiliated to Medical College of Southeast University, Wuxi, China
| | - Zhenguo Zhao
- Department of General Surgery, Jiangyin Hospital Affiliated to Medical College of Southeast University, Wuxi, China
| | - Qi Sun
- Department of General Surgery, Jiangyin Hospital Affiliated to Medical College of Southeast University, Wuxi, China
| | - Guoyi Shao
- Department of General Surgery, Jiangyin Hospital Affiliated to Medical College of Southeast University, Wuxi, China
| | - Jianming Huang
- Department of General Surgery, Jiangyin Hospital Affiliated to Medical College of Southeast University, Wuxi, China
| | - Wei Zhao
- Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong, SAR, China
| | - Yuting Kuang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
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Liu Y, Cao J, Pu YS, Ma Y, Wu M, Wang JH. RP11-874J12.4, a novel lncRNA, confers chemoresistance in human gastric cancer cells by sponging miR-3972 and upregulating SSR2 expression. Am J Transl Res 2021; 13:5892-5910. [PMID: 34306333 PMCID: PMC8290636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 01/19/2021] [Indexed: 06/13/2023]
Abstract
Increasing evidence has revealed the contributions of long noncoding RNAs (lncRNAs) in the modulation of drug resistance in gastric cancer. In the present study, we explored the role of a novel lncRNA, RP11-874J12.4, in regulating chemoresistance in gastric cancer and determined the underlying molecular mechanisms. We observed that compared with normal controls, human gastric cancer tissues and cell lines, including MKN-45 and AGS cells, expressed higher RP11-874J12.4 levels. RP11-874J12.4 knockdown sensitized MKN-45 and AGS cells to docetaxel and cisplatin in terms of cell viability and apoptosis rate. In addition, RP11-874J12.4 was found to be a competing endogenous RNA that sponged microRNA (miR)-3972, which showed significantly reduced expression in human gastric cancer tissues and cell lines. Furthermore, signal sequence receptor subunit 2 (SSR2) was identified as a downstream target of miR-3972, and the miR-3972/SSR2 axis was found to regulate chemoresistance in MKN-45 and AGS cells. SSR2 downregulation further sensitized gastric cancer cells with RP11-874J12.4 knockdown to chemotherapeutic drugs via enhanced apoptosis, which was evidenced by significantly upregulated expressions of cleaved caspase-3, cleaved caspase-9, and Bax and downregulated expression of Bcl-2. Furthermore, RP11-874J12.4 knockdown markedly inhibited the growth of xenograft MKN-45 cells in nude mice, which was associated with an increased expression of miR-3972 and decreased expression of SSR2 in tumors. Therefore, the RP11-874J12.4/miR-3972/SSR2 axis plays important roles in the regulation of chemoresistance in MKN-45 and AGS cells and may serve as a target for the diagnosis and treatment of human gastric cancer.
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Affiliation(s)
- Yi Liu
- Department of Oncology, Shaanxi Provincial People’s HospitalXi’an 710068, China
| | - Jian Cao
- Department of Gastroenterology, 986 Hospital of PLAXi’an 710054, China
| | - Yan-Song Pu
- Department 2 of General Surgery, Shaanxi Provincial People’s HospitalXi’an 710068, China
| | - Yu Ma
- Department of Pathology, Shaanxi Provincial People’s HospitalXi’an 710068, China
| | - Min Wu
- Office of Academic Research, Shaanxi Provincial People’s HospitalXi’an 710068, China
| | - Jian-Hua Wang
- Department 2 of General Surgery, Shaanxi Provincial People’s HospitalXi’an 710068, China
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14
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Xu Z, Peng B, Cai Y, Wu G, Huang J, Gao M, Guo G, Zeng S, Gong Z, Yan Y. N6-methyladenosine RNA modification in cancer therapeutic resistance: Current status and perspectives. Biochem Pharmacol 2020; 182:114258. [PMID: 33017575 DOI: 10.1016/j.bcp.2020.114258] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 09/25/2020] [Accepted: 09/29/2020] [Indexed: 02/05/2023]
Abstract
Several strategies, including chemotherapy and radiotherapy, have improved therapeutic outcomes among cancer patients in clinical practice. However, due to their heterogeneity, cancer cells frequently display primary or acquired therapeutic resistance, thereby resulting in treatment failure. The mechanisms underlying cancer therapeutic resistance are complex and varied. Among them, N6-methyladenosine (m6A) RNA modification has gained increasing attention as a potential determinant of therapy resistance within various cancers. In this review, we primarily describe evidence for the effect of the m6A epitranscriptome on RNA homeostasis modulation, which has been shown to alter multiple cellular pathways in cancer research and treatment. Additionally, we discuss the profiles and biological implications of m6A RNA methylation, which is undergoing intensive investigation for its effect on the control of therapeutic resistance.
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Affiliation(s)
- Zhijie Xu
- Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | - Bi Peng
- Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
| | - Yuan Cai
- Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
| | - Geting Wu
- Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
| | - Jinzhou Huang
- Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | - Ming Gao
- Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | - Guijie Guo
- Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | - Shuangshuang Zeng
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
| | - Zhicheng Gong
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
| | - Yuanliang Yan
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
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15
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Ramezankhani R, Solhi R, Es HA, Vosough M, Hassan M. Novel molecular targets in gastric adenocarcinoma. Pharmacol Ther 2020; 220:107714. [PMID: 33172596 DOI: 10.1016/j.pharmthera.2020.107714] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 10/19/2020] [Indexed: 02/06/2023]
Abstract
Gastric adenocarcinoma (GAC) is the third leading cause of cancer-related death worldwide. A high mortality rate and resistance to treatment protocols due to a heterogeneous molecular pathogenesis has made discovering the key etiologic molecular alterations of the utmost importance. The remarkable role played by epigenetic modifications in repressing or activating many cancer-related genes and forming new epigenetic signatures can affect cancer initiation and progression. Hence, targeting the key epigenetic drivers could potentially attenuate cancer progression. MLLs, ARID1A and EZH2 are among the major epigenetic players that are frequently mutated in GACs. In this paper, we have proposed the existence of a network between these proteins that, together with PCAF and KDM6A, control the 3D chromatin structure and regulate the expression of tumor suppressor genes (TSGs) and oncogenes in GAC. Therefore, we suggest that manipulating the expression of EZH2, PCAF, and KDM6A or their downstream targets may reduce the cancerous phenotype in GAC.
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Affiliation(s)
- Roya Ramezankhani
- Department of Applied Cell Sciences, Faculty of Basic Science and Advanced Medical Technologies, Royan Institute, ACECR, Tehran, Iran; Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven Stem Cell Institute, Leuven, Belgium
| | - Roya Solhi
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran; Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | | | - Massoud Vosough
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, ACECR, Tehran, Iran.
| | - Moustapha Hassan
- Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; ECM, Clinical research center (KFC), Karolinska University Hospital Huddinge, Sweden.
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BC032913 as a Novel Antisense Non-coding RNA is Downregulated in Gastric Cancer. J Gastrointest Cancer 2020; 52:928-931. [DOI: 10.1007/s12029-020-00517-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Abstract
PURPOSE OF REVIEW Although extensively studied for over a decade, gene expression programs established at the epigenetic and/or transcriptional levels do not fully characterize cancer stem cells (CSC). This review will highlight the latest advances regarding the functional relevance of different key post-transcriptional regulations and how they are coordinated to control CSC homeostasis. RECENT FINDINGS In the past 2 years, several groups have identified master post-transcriptional regulators of CSC genetic programs, including RNA modifications, RNA-binding proteins, microRNAs and long noncoding RNAs. Of particular interest, these studies reveal that different post-transcriptional mechanisms are coordinated to control key signalling pathways and transcription factors to either support or suppress CSC homeostasis. SUMMARY Deciphering molecular mechanisms coordinating plasticity, survival and tumourigenic capacities of CSCs in adult and paediatric cancers is essential to design new antitumour therapies. An entire field of research focusing on post-transcriptional gene expression regulation is currently emerging and will significantly improve our understanding of the complexity of the molecular circuitries driving CSC behaviours and of druggable CSC weaknesses.
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Du W, Sun J, Gu J, Zhang S, Zhang T. Bioinformatics analysis of LINC00426 expression in lung cancer and its correlation with patients' prognosis. Thorac Cancer 2020; 11:150-155. [PMID: 31691516 PMCID: PMC6938767 DOI: 10.1111/1759-7714.13228] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 10/04/2019] [Accepted: 10/04/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND To investigate the expression of long noncoding RNA (lncRNA) LINC00426 (long intergenic nonprotein coding RNA 426) in non-small cell lung cancer (NSCLC) patients and its correlation with their prognosis. METHODS The expression of long noncoding RNA LINC00426 of non-small cell lung cancer (NSCLC) in The Cancer Genome Atlas (TCGA) database was screened. According to the expression level of LINC00426 in tumor tissue of NSCLC patients, the patients were divided into high and low LINC00426 expression groups. The correlation between LINC00426 expression group and the prognosis of the patient was analyzed by log-rank test. A total of 72 NSCLC patients who had undergone surgery were retrospectively included in this study. LINC00426 relative expression of tumor and normal lung tissue of the included 72 NSCLC patients were examined by real-time quantitative PCR assay. The correlation between LINC00426 expression and the patients' clinical characteristics were also evaluated. RESULTS LINC00426 relative expression was not statistically different between cancer and normal tissue (P > 0.05) of NSCLC patients in the TCGA database. The amplification and deep deletion mutation of LINC00426 gene was found in 0.5% of NSCLC patients. The overall survival (OS) of the LINC00426 high expression group was significantly higher than that of the low expression group (HR = 0.81, P = 0.044), while there was no significant difference between the high and low expression group (HR = 0.97, P = 0.82) for disease-free survival (DFS). LINC0042646 expression level was elevated in 46 cases in normal lung tissue compared to the tumor tissue of the 72 NSCLC patients. LINC0042646 expression level was significantly correlated with the clinical stage (P < 0.05). CONCLUSION Long noncoding RNA LINC00426 was downregulated in the tumor tissue of NSCLC patients and correlated with poor prognosis.
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Affiliation(s)
- Wenjun Du
- Department of Spine CenterTianjin Union Medical Center (Tianjin People's Hospital)TianjinChina
| | - Juan Sun
- Department of RadiologyTianjin Union Medical Center (Tianjin People's Hospital)TianjinChina
| | - Jundong Gu
- Department of Thoracic SurgeryTianjin Union Medical Center (Tianjin People's Hospital)TianjinChina
| | - Shiwu Zhang
- Department of PathologyTianjin Union Medical Center (Tianjin People's Hospital)TianjinChina
| | - Tao Zhang
- Department of TraumaTianjin HospitalTianjinChina
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19
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Yu H, Yang AM, Lu XH, Feng L, Wu X, Cui JF, Cheng JY. Analysis of Long Non-Coding RNA Expression Profile and Functional Study of LOC389332 in Early Gastric Cancer. Med Sci Monit 2019; 25:10114-10121. [PMID: 31884510 PMCID: PMC6948287 DOI: 10.12659/msm.917935] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background Long non-coding RNAs (LncRNAs) could potentially function as diagnostic markers for gastric carcinoma. Nevertheless, the expression profile and biological feature of LncRNAs in early gastric cancer (EGC) remains to be explored. Material/Methods LncRNA expression microarray analysis was performed on 6 paired EGC tissues. One deregulated LncRNA, LOC389332, was validated using a quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay using independent tissue samples and cell lines. The Cell Counting Kit-8 (CCK-8) assay and wound healing assay were conducted to evaluate its influences on the proliferation and migration of gastric cancer cells. LncRNA expression microarray and gene ontology (GO) analysis were also performed on the LOC389332 knockdown cell line model to explore the molecular feature of LOC389332 in gastric carcinoma. Results The LncRNA expression profiling showed that 72 LncRNAs were significantly differentially expressed in EGC tissues. The results in the validation phase revealed that LOC389332 was remarkably overexpressed in gastric carcinoma tissues, precancerous lesions, and gastric cancer cells. Functional study showed that knockdown of LOC389332 expression could inhibit cell proliferation and migration. LncRNA expression microarray on the LOC389332 knockdown cell line model revealed that 393 mRNAs were differentially expressed. The GO enrichment analysis indicated that the downregulated genes were mainly associated with cell membrane function, signal transmission process, and cell adhesion process. Conclusions The LncRNA expression profile between EGC and gastritis tissues was significantly different. LOC389332 was potential non-coding oncogenes in gastric cancer, and it may perform its function through altering cell membrane function, signal transmission, and cell adhesion.
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Affiliation(s)
- Hang Yu
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (mainland)
| | - Ai-Ming Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (mainland)
| | - Xing-Hua Lu
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (mainland)
| | - Lin Feng
- State Key Laboratory of Molecular Oncology, Cancer Institute Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (mainland)
| | - Xi Wu
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (mainland)
| | - Jian-Fang Cui
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (mainland)
| | - Jie-Yao Cheng
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (mainland)
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Ge H, Yan Y, Yue C, Liang C, Wu J. Long Noncoding RNA LINC00265 Targets EGFR and Promotes Deterioration of Colorectal Cancer: A Comprehensive Study Based on Data Mining and in vitro Validation. Onco Targets Ther 2019; 12:10681-10692. [PMID: 31824175 PMCID: PMC6901053 DOI: 10.2147/ott.s227482] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 11/21/2019] [Indexed: 12/12/2022] Open
Abstract
Background LncRNAs are found to be aberrantly expressed in human cancers and could function as potential oncogenes or tumor suppressor genes. LINC00265 is a newly discovered LncRNA and its function in colorectal cancer (CRC) remains unknown. Methods Comprehensive bioinformatics analysis were performed to investigate the expression, clinical significance and potential biologic functions of LINC00265 in CRC based on the data from the Cancer Genome Atlas (TCGA). To further investigate the potential role of LINC00265 in CRC, we knocked down the LINC00265 expression in HT29 cells. The cell proliferation, invasion, cycle distribution, and apoptosis were evaluated in control, NC and siRNA groups. Additionally, effect of LINC00265 on the expression of EGFR was also measured. Results The expression level of LINC00265 is increased in CRC tissues. Elevated level of LINC00265 is correlated with lymph node metastases and advanced pathological stage. We obtained 269 LINC00265 related genes; the results of functional analysis of these genes revealed that LINC00265 might involve in carcinogenesis of CRC. In addition, further experiments indicated that LINC00265 knockdown impaired cell proliferation and invasion, promoted cell cycle distribution and apoptosis in HT29 cells. Moreover, Western blot analysis revealed that downregulation of LINC00265 suppressed the expression of EGFR. Conclusion Our results indicate that LINC00265 induces cell proliferation, migration and inhibits CRC cells apoptosis by targeting EGFR. LINC00265 could be served as a diagnostic factor and therapeutic target for CRC patients.
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Affiliation(s)
- Hua Ge
- Department of Gastrointestinal Surgery, The First People's Hospital of Zunyi, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People's Republic of China
| | - Yan Yan
- Quality Control Department, The First People's Hospital of Zunyi, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People's Republic of China
| | - Chaosen Yue
- Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Chaojie Liang
- Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China
| | - Jixiang Wu
- Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China
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Overexpression of PURPL and downregulation of NONHSAT062994 as potential biomarkers in gastric cancer. Life Sci 2019; 237:116904. [PMID: 31606380 DOI: 10.1016/j.lfs.2019.116904] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 09/18/2019] [Accepted: 09/22/2019] [Indexed: 02/07/2023]
Abstract
AIMS Long non-coding RNAs (LncRNAs) play central roles in the formation and development of gastric cancer (GC). The aim of this study was to evaluate the expression of PURPL and NONHSAT062994 and the relationship between their expressions with clinical characteristics in GC. MAIN METHODS PURPL and NONHSAT062994 LncRNAs and p53 gene expression levels were analyzed both in 50 pairs of cancerous and adjacent noncancerous tissue samples in GC patients using qRT-PCR and in four sets of data obtained from Gene Expression Omnibus (GEO) database. Chi-square (χ2) test was used to determine the relationship between PURPL, NONHSAT062994 RNA levels and the clinicopathological characteristics of GC. Receiver operating characteristic (ROC) curves were drawn to represent sensitivity and specificity of PURPL and NONHSAT062994 expression as markers of GC. KEY FINDINGS Expression of PURPL was significantly upregulated in 50 GC samples as well as in GC tissues from GSE13911 and GSE27342 datasets. Our results demonstrated that PURPL RNA level in GC was significantly related to tumor size and histopathological grade. p53 expression at both protein and mRNA levels were significantly decreased in GC tissues compared to adjacent control samples. NONHSAT062994 expression was downregulated in 50-pair GC and GC tissues from GSE13915 dataset. However, NONHSAT062994 showed no consistently differential expression in GSE2637dataset. NONHSAT062994 was significantly associated with histological grade and tumor size. SIGNIFICANCE Overall, these results suggest that PURPL and NONHSAT062994 may play critical roles in the progression of GC and therefore might be considered as candidate tumor markers for therapeutic goals.
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Wu X, Liu X. Analysis of the expression of D-dimer, CD147 and miR203 and their correlation in gastric cancer. Pak J Med Sci 2019; 35:443-447. [PMID: 31086530 PMCID: PMC6500820 DOI: 10.12669/pjms.35.2.718] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Objectives: To evaluate the relationship of D-dimer, CD147 and miR-203, and detect the influence of these biomarkers on the pathological characteristics in patients with gastric cancer. Methods: The patients with gastric cancer treated using radical gastrectomy between May 2013 and October 2017 were reviewed retrospectively. The expression of D-dimer, miR203 and CD147 was measured for all the patients, and the clinical data including age, gender, tumor size, tumor differentiation, invasion depth, lymphatic metastasis, TMN stage, and pathological type were retrieved and analyzed. The study was carried out in affiliated Yidu Central Hospital of Weifang Medical College, Qingzhou, China. Results: Two hundred sixty patients with gastric cancer were included. The patients with tumor metastasis, larger tumor diameter, lower differentiation, lymphatic metastasis, deeper invasion, and higher TMN stage presented with a significantly higher D-dimer and CD 147 expression, but the level of the two biomarkers didn’t show a significant difference in patients with different pathological type, gender and age. Compared with CD147 and D-dimer, miR203 presented with different characteristics of expression. In addition, the expression of miR203 was negatively correlated with CD147 and D-dimer, and there was a positive correlation between CD147 and D-dimer in patients with gastric cancer. Conclusion: In this study, a close correlation of D-dimer, miR203 and CD147 was found, and these three biomarkers should be screened in gastric cancer patients.
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Affiliation(s)
- Xiguo Wu
- Xiguo Wu, Department of Laboratory, Affiliated Yidu Central Hospital of Weifang Medical College, Qingzhou, 262500, China
| | - Xiuzhen Liu
- Xiuzhen Liu, Department of Functional Inspection, Affiliated Yidu Central Hospital of Weifang Medical College, Qingzhou, 262500, China
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Oncogenicity of lncRNA FOXD2-AS1 and its molecular mechanisms in human cancers. Pathol Res Pract 2019; 215:843-848. [PMID: 30723052 DOI: 10.1016/j.prp.2019.01.033] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Revised: 01/06/2019] [Accepted: 01/25/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Long non-coding RNAs (lncRNAs) are a group of noncoding RNAs with length larger than 200 nucleotides. LncRNAs have limited or no protein-coding capacity because of lack of obvious open reading frame. An increasing number of researches have shown that lncRNAs participate in the complex regulation network of cancer and play an important role in tumourigenesis and progression such as proliferation, migration and invasion. LncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1), located on chromosome 1p33 and with a transcript length of 2527 nucleotides, is a novel cancer-related lncRNA. FOXD2-AS1 was recently found to exhibit aberrant expression in various malignancies, including gastric, lung, bladder, colorectal, nasopharyngeal, esophageal, hepatocellular, thyroid and skin cancer, and its deregulation might be related to survival and prognosis of cancer patients. Pertinent to clinical practice, FOXD2-AS1 might act as a feasible biomarker or therapeutic target in human cancers. In this paper, we made a summary on the current findings concerning the biological functions and molecular mechanisms of FOXD2-AS1 in tumor progression. MATERIALS AND METHODS In this paper, we summarized and figured out recent studies about the expression and molecular biological mechanisms of FOXD2-AS1 in tumor progression. Existing relevant studies were obtained through a systematic search from PubMed, Embase, BioMedNet, GEO database and Cochrane Library. RESULTS FOXD2-AS1 was a valuable tumor-associated lncRNA. Its expression level was up-regulation in various malignancies, including gastric, lung, bladder, colorectal, nasopharyngeal, esophageal, hepatocellular, thyroid and skin cancer. In addition, the aberrant expressions of FOXD2-AS1 have shown to contribute to proliferation, migration and invasion of cancer cells, and its deregulation is related to carcinogensis, overall survival, disease free survival, prognosis and tumor progression. CONCLUSIONS LncRNA FOXD2-AS1 is an oncogene and probably represents a feasible biomarker or therapeutic target in human cancers.
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