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MicroRNA-451a targets caveolin-1 in stomach cancer cells.

ABSTRACT: MicroRNA-451 (miR-451) is lowly expressed in stomach cancer cells and improves their metastatic ability by down-regulating extracellular signal-regulated kinase 2 (ERK2). Many studies have found that caveolin-1 (CAV1) plays an important role in cancer progression. Additionally, miR-451 has been reported to regulate the expression of CAV1 in chronic obstructive pulmonary disease. Therefore, this study aims to determine if miR-451 regulates the biological functions of stomach cancer cells by regulating CAV1 expression. Through a bioinformatics analysis, we found that miR-451a regulates CAV1 expression, and miR-451a expression is relatively low in stomach cancer cells. Next, we confirmed that miR-451a negatively regulates CAV1 expression using a dual-luciferase reporter assay. Then MTT, 5-ethynyl-2'-deoxyuridine (EdU), propidium iodide (PI), an Annexin V-FITC/PI apoptosis kit, and transwell assays were used to measure the changes in cell proliferation, the cell cycle, apoptosis, cell migration, and invasiveness in stomach cancer cells overexpressing miR-451a or both miR-451a and CAV1. It was found that increasing the miR-451a expression in stomach cancer cells inhibits cell growth, migration, and invasiveness, and promotes apoptosis. After restoring the CAV1 expression, these biological processes resumed. In summary, in stomach cancer cells, the overexpression of miR-451a can restrain cell growth and promote apoptosis, so it is a potential treatment for stomach cancer.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7642723 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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MicroRNA-451a targets caveolin-1 in stomach cancer cells.

Wang Yi Y Lin Zhenmeng Z Song Jintian J Wei Shenghong S Ye Zaisheng Z Chen Shu S Zeng Yi Y Lin Zhitao Z Chen Xiaoling X Chen Luchuan L

International journal of clinical and experimental pathology 20201001 10

MicroRNA-451 (miR-451) is lowly expressed in stomach cancer cells and improves their metastatic ability by down-regulating extracellular signal-regulated kinase 2 (ERK2). Many studies have found that caveolin-1 (CAV1) plays an important role in cancer progression. Additionally, miR-451 has been reported to regulate the expression of CAV1 in chronic obstructive pulmonary disease. Therefore, this study aims to determine if miR-451 regulates the biological functions of stomach cancer cells by regul ...[more]

PMID: 33165443

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Project description:BackgroundColorectal cancer (CRC) is a leading cause of cancer-related death. The biologic response of CRC to standard of care adjuvant therapies such as chemotherapy and radiation are poorly understood. MicroRNAs (miRs) have been shown to affect CRC progression and metastasis. Therefore, we hypothesized that specific miRs modulate CRC response to chemoradiation.MethodsIn this study, we used miR expression profiling and discovered a set of microRNAs upregulated rapidly in response to either a single 2 Gy dose fraction or a 10 Gy dose of γ-radiation in mouse colorectal carcinoma models. We used gain and loss-of-function studies in 2D and 3Dcell proliferation assays and colony formation assays to understand the role of the top miR candidate from our profiling. We used Student's T-tests for simple comparisons and two-factor ANOVA for evaluating significance.ResultsThe most upregulated candidate at early time points in our signature, miR-451a inhibited tumor cell proliferation and attenuated surviving fraction in longer-term cultures. Conversely, inhibition of miR-451a increased proliferation, tumorsphere formation, and surviving fraction of tumor cells. Using a bioinformatics approach, we identified four genes, CAB39, EMSY, MEX3C, and EREG, as targets of miR-451a. Transfection of miR-451a decreased both mRNA and protein levels of these targets. Importantly, we found miR-451a expression was high and CAB39, EMSY levels were low in a small subset of rectal cancer patients who had a partial response to chemoradiation when compared to patients that had no response. Finally, analysis of a TCGA colorectal cancer dataset revealed that CAB39 and EMSY are upregulated at the protein level in a significant number of CRC patients. Higher levels of CAB39 and EMSY correlated with poorer overall survival.ConclusionsTaken together, our data indicates miR-451a is induced by radiation and may influence colorectal carcinoma proliferation via CAB39 and EMSY pathways.

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MicroRNA-451a targets caveolin-1 in stomach cancer cells.

Publications

MicroRNA-451a targets caveolin-1 in stomach cancer cells.

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