Effects of miR-1236-3p and miR-370-5p on activation of p21 in various tumors and its inhibition on the growth of lung cancer cells

The mechanism of dsRNA-induced gene activation (RNAa) is being gradually unveiled. The plentiful evidence that it existed in mammalian species other than human demonstrated that dsRNA-mediated RNAa is a conservative phenomenon. Simultaneously, accumulating evidence suggested that microRNAs could act...

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Main Authors: Chuanchang Li, Qiangqiang Ge, Jiaxuan Liu, Qingsong Zhang, Chenghe Wang, Kai Cui, Zhong Chen
Format: Article
Language:English
Published: SAGE Publishing 2017-06-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317710824
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author Chuanchang Li
Qiangqiang Ge
Jiaxuan Liu
Qingsong Zhang
Chenghe Wang
Kai Cui
Zhong Chen
author_facet Chuanchang Li
Qiangqiang Ge
Jiaxuan Liu
Qingsong Zhang
Chenghe Wang
Kai Cui
Zhong Chen
author_sort Chuanchang Li
collection DOAJ
description The mechanism of dsRNA-induced gene activation (RNAa) is being gradually unveiled. The plentiful evidence that it existed in mammalian species other than human demonstrated that dsRNA-mediated RNAa is a conservative phenomenon. Simultaneously, accumulating evidence suggested that microRNAs could activate gene expression by targeting promoter. Nevertheless, it is ambiguous whether microRNA-induced gene activation in different human cells is a common phenomenon. The study we performed verified that miR-1236-3p (miR-1236) and miR-370-5p can activate p21 expression in bladder cancer (BCa) T24, EJ cells, and non-small-cell lung carcinoma A549 cells, while in hepatocellular HepG2 cells both microRNAs cannot effectively induce the expression of P21 WAF1/CIP1 (p21). In pancreatic cancer PANC-1 cells, only miR-370-5p had the potent abilities to induce p21 expression rather than miR-1236-3p. Unlike microRNA-mediated RNA activation, we can observe that dsP21-322 significantly activated p21 in above cells. Besides, we demonstrated that miR-1236 and miR-370 inhibited cyclin D1-CDK4/CDK6 pathway while upregulated E-cadherin expression by upregulation of p21 . Overexpression of these two microRNAs in A549 induced cell-cycle arrest and cell senescence, delayed cell proliferation and colony formation, and inhibited migration and invasion. In conclusion, microRNA-mediated RNAa depends on the cell context, and miR-1236 and miR-370 can inhibit non-small-cell lung carcinoma cell growth by upregulating p21 expression in vitro.
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spelling doaj-art-852635fa24544be699fc2402ca98ea9c2025-08-20T03:36:57ZengSAGE PublishingTumor Biology1423-03802017-06-013910.1177/1010428317710824Effects of miR-1236-3p and miR-370-5p on activation of p21 in various tumors and its inhibition on the growth of lung cancer cellsChuanchang Li0Qiangqiang Ge1Jiaxuan Liu2Qingsong Zhang3Chenghe Wang4Kai Cui5Zhong Chen6Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Urology, Zhongnan Hospital, Wuhan University, Wuhan, ChinaDepartment of Pathology, Changzheng Hospital, The Second Military Medical University, Shanghai, ChinaDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaThe mechanism of dsRNA-induced gene activation (RNAa) is being gradually unveiled. The plentiful evidence that it existed in mammalian species other than human demonstrated that dsRNA-mediated RNAa is a conservative phenomenon. Simultaneously, accumulating evidence suggested that microRNAs could activate gene expression by targeting promoter. Nevertheless, it is ambiguous whether microRNA-induced gene activation in different human cells is a common phenomenon. The study we performed verified that miR-1236-3p (miR-1236) and miR-370-5p can activate p21 expression in bladder cancer (BCa) T24, EJ cells, and non-small-cell lung carcinoma A549 cells, while in hepatocellular HepG2 cells both microRNAs cannot effectively induce the expression of P21 WAF1/CIP1 (p21). In pancreatic cancer PANC-1 cells, only miR-370-5p had the potent abilities to induce p21 expression rather than miR-1236-3p. Unlike microRNA-mediated RNA activation, we can observe that dsP21-322 significantly activated p21 in above cells. Besides, we demonstrated that miR-1236 and miR-370 inhibited cyclin D1-CDK4/CDK6 pathway while upregulated E-cadherin expression by upregulation of p21 . Overexpression of these two microRNAs in A549 induced cell-cycle arrest and cell senescence, delayed cell proliferation and colony formation, and inhibited migration and invasion. In conclusion, microRNA-mediated RNAa depends on the cell context, and miR-1236 and miR-370 can inhibit non-small-cell lung carcinoma cell growth by upregulating p21 expression in vitro.https://doi.org/10.1177/1010428317710824
spellingShingle Chuanchang Li
Qiangqiang Ge
Jiaxuan Liu
Qingsong Zhang
Chenghe Wang
Kai Cui
Zhong Chen
Effects of miR-1236-3p and miR-370-5p on activation of p21 in various tumors and its inhibition on the growth of lung cancer cells
Tumor Biology
title Effects of miR-1236-3p and miR-370-5p on activation of p21 in various tumors and its inhibition on the growth of lung cancer cells
title_full Effects of miR-1236-3p and miR-370-5p on activation of p21 in various tumors and its inhibition on the growth of lung cancer cells
title_fullStr Effects of miR-1236-3p and miR-370-5p on activation of p21 in various tumors and its inhibition on the growth of lung cancer cells
title_full_unstemmed Effects of miR-1236-3p and miR-370-5p on activation of p21 in various tumors and its inhibition on the growth of lung cancer cells
title_short Effects of miR-1236-3p and miR-370-5p on activation of p21 in various tumors and its inhibition on the growth of lung cancer cells
title_sort effects of mir 1236 3p and mir 370 5p on activation of p21 in various tumors and its inhibition on the growth of lung cancer cells
url https://doi.org/10.1177/1010428317710824
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