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Long non-coding RNA-ZNF281 promotes cancer cell migration and invasion in gastric cancer via downregulation of microRNA-124.

ABSTRACT: It has previously been determined that long non-coding (lnc)RNA-zinc finger protein (ZNF)281 serves an oncogenic role in breast cancer; however, the role of lncRNA-ZNF281 in other cancer types is yet to be elucidated. The present study aimed to analyze the role of ZNF281 in gastric cancer by characterizing its activity in cancerous tissues and normal tissues using RT-qPCR. Overexpression experiments were also performed to investigate the interaction between ZNF281 and miR-124, and Transwell assays were conducted to analyze cell invasion and migration. The present study revealed that lncRNA-ZNF281 was upregulated, and that microRNA (miR)-124 was downregulated, in cancerous tissues compared with that in the paired adjacent healthy tissues of patients with gastric cancer. In addition, the expression levels of lncRNA-ZNF281 and miR-124 exhibited a significant inverse association. Furthermore, in vitro cell experiments determined that lncRNA-ZNF281 overexpression resulted in miR-124 inhibition, yet miR-124 overexpression did not influence lncRNA-ZNF281 expression. lncRNA-ZNF281 expression level was also associated with the clinical stage of the patient. Bioinformatics analysis revealed that lncRNA-ZNF281 may target the base pairs in the hairpin loop of the miR-124 precursor. Subsequent in vitro cell experiments indicated that lncRNA-ZNF281 overexpression resulted in promoting the migration and invasiveness of gastric cancer cells, while miR-124 over-expression led to its inhibition. In addition, miR-124 overexpression partially recovered the effects of lncRNA-ZNF281 overexpression. Therefore, lncRNA-ZNF281 may promote cancer cell migration and invasion in gastric cancer via downregulation of miR-124.

SUBMITTER: Gao H

PROVIDER: S-EPMC7039167 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Long non-coding RNA-ZNF281 promotes cancer cell migration and invasion in gastric cancer via downregulation of microRNA-124.

Gao Hengling H Li Peizhe P Hei Yingrui Y Li Shuliang S Wang Jinkai J Lv Xukun X Zhang Jianxian J

Oncology letters 20200110 3

It has previously been determined that long non-coding (lnc)RNA-zinc finger protein (ZNF)281 serves an oncogenic role in breast cancer; however, the role of lncRNA-ZNF281 in other cancer types is yet to be elucidated. The present study aimed to analyze the role of ZNF281 in gastric cancer by characterizing its activity in cancerous tissues and normal tissues using RT-qPCR. Overexpression experiments were also performed to investigate the interaction between ZNF281 and miR-124, and Transwell assa ...[more]

PMID: 32194679

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Project description:BackgroundIncreasing evidence has suggested that dysregulation of certain microRNAs (miRNAs) may contribute to human disease including carcinogenesis and tumor metastasis in human. miR-124-3p is down-regulated in various cancers, and modulates proliferation and aggressiveness of cancer cells. However, the roles of miR-124-3p in human bladder cancer are elusive. Thus, this study was conducted to investigate the biological functions and its molecular mechanisms of miR-124-3p in human bladder cancer cell lines, discussing whether it has a potential to be a therapeutic biomarker of bladder cancer.MethodsThree human bladder cancer cell lines and samples from ten patients with bladder cancer were analyzed for the expression of miR-124-3p by quantitative RT--PCR. Exogenetic overexpression of miR-124-3p was established by transfecting mimics into T24, UM-UC-3 and J82 cells, after that cell proliferation and cell cycle were assessed by MTT assay, flow cytometry and Colony-forming assay. Cell motility and invasion ability were evaluated by wound healing assay and transwell assay. Tissue microarray, and immunohistochemistry with antibodies against ROCK1, MMP2 and MMP9 was performed using the peroxidase and DAB methods. The target gene of miR-124-3p was determined by luciferase assays, quantitative RT--PCR and western blot. The regulation of epithelial-to-mesenchymal transition by miR-124-3p was analyzed by western blot.ResultsmiR-124-3p is frequently down-regulated in bladder cancer both in three bladder cancer cell lines, T24, UM-UC-3, J82 and clinical samples. Overexpression of miR-124-3p induced G1-phase arrest in T24, UM-UC-3 and J82 cell lines and suppressed cell growth in colony-forming assay. miR-124-3p significantly repressed the capability of migration and invasion of bladder cancer cells. In addition, ROCK1 was identified as a new target of miR-124-3p. ROCK1, MMP2, MMP9 were up-regulated in bladder cancer tissues. Furthermore, we demonstrated miR-124-3p could inhibit bladder cancer cell epithelial mesenchymal transfer, and regulated the expression of c-Met, MMP2, MMP9.ConclusionsmiR-124-3p can repress the migration and invasion of bladder cancer cells via regulating ROCK1. Our data indicate that miR-124-3p could be a tumor suppressor and may have a potential to be a diagnostics or predictive biomarker in bladder cancer.

Dataset Information

Long non-coding RNA-ZNF281 promotes cancer cell migration and invasion in gastric cancer via downregulation of microRNA-124.

Publications

Long non-coding RNA-ZNF281 promotes cancer cell migration and invasion in gastric cancer via downregulation of microRNA-124.

Similar Datasets

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