MiR-146a-5p inhibits cell proliferation and cell cycle progression in NSCLC cell lines by targeting CCND1 and CCND2
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Yan-Li Li1,*, Ju Wang1,*, Cai-Yan Zhang1,*, Yu-Qing Shen1, Hui-Min Wang1, Lei Ding1, Yu-Chen Gu1, Jia-Tao Lou2, Xin-Tai Zhao3, Zhong-Liang Ma1, You-Xin Jin1
1School of Life Sciences, Shanghai University, Shanghai 200444, China
2Department of Laboratory Medicine, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200030, China
3Shanghai Shines Pharmaceuticals Co., Ltd., Shanghai 200032, China
*These authors contributed equally to this work
You-Xin Jin, email: [email protected]
Zhong-Liang Ma, email: [email protected]
Keywords: miR-146a-5p, non-small cell lung cancer, tumor suppressor gene, cell cycle, CCND1
Received: March 02, 2016 Accepted: June 03, 2016 Published: August 03, 2016
Previous studies have indicated that miR-146a-5p acts as an oncogene in several types of cancer, yet a tumor suppressor gene in others. In non-small cell lung cancer (NSCLC), one report showed that it was downregulated and played the role of tumor suppressor. However, another study showed that miR-146a-5p was overexpressed in the serum of NSCLC patients compared to healthy controls. Therefore, it is obvious that further study of the function of miR-146a-5p in NSCLC is necessary to fully understand its importance. Herein, we have verified that miR- 146a- 5p acts as a tumor suppressor in NSCLC. Our data revealed that the expression level of miR-146a-5p was significantly decreased in several human NSCLC cell lines, and also less abundant in human NSCLC tissues, when compared with controls. Moreover, we observed that miR-146a-5p could suppress cell proliferation, both in vitro and in vivo. Our results also showed that miR-146a-5p directly targeted the 3′-UTR of CCND1 and CCND2 mRNAs as well as decreased their expression at both mRNA and protein levels, causing cell cycle arrest at the G0/G1 phase. Furthermore, siRNA-mediated downregulation of CCND1 or CCND2 yielded the same effects on proliferation and cell cycle arrest as miR-146a-5p upregulation did in the NSCLC cell lines. We confirmed that the expression of miR-146a-5p had negative relationship with CCND1 or CCND2. Besides, we also found that miR-146a-5p could inhibit tumor growth in xenograft mouse models, and CCND1 and CCND2 were downregulated in miR-146a-5p overexpressed xenograft tumor tissues. In summary, our results demonstrated that miR-146a-5p could suppress the proliferation and cell cycle progression in NSCLC cells by inhibiting the expression of CCND1 and CCND2.
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