title: MiR-146a-5p inhibits cell proliferation and cell cycle progression in NSCLC cell lines by targeting CCND1 and CCND2.
abstract: 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 xengroft mouse models, and CCND1 and CCND2 were downregulated in miR-146a-5p overexpressed xengroft 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.
authors: School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors: Yan-Li
authors: YL
authors: Li
authors: School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors: Ju
authors: J
authors: Wang
authors: School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors: Cai-Yan
authors: CY
authors: Zhang
authors: School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors: Yu-Qing
authors: YQ
authors: Shen
authors: School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors: Hui-Min
authors: HM
authors: Wang
authors: School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors: Lei
authors: L
authors: Ding
authors: School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors: Yu-Chen
authors: YC
authors: Gu
authors: Department of Laboratory Medicine, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200030, China.
authors: Jia-Tao
authors: JT
authors: Lou
authors: Shanghai Shines Pharmaceuticals Co., Ltd., Shanghai 200032, China.
authors: Xin-Tai
authors: XT
authors: Zhao
authors: School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors: Zhong-Liang
authors: ZL
authors: Ma
authors: School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors: You-Xin
authors: YX
authors: Jin
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000628:therapy*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; C530104:CCND1 protein, human; C080336:CCND2 protein, human; D056742:Cyclin D2; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D019938:Cyclin D1
keywords: CCND1; cell cycle; miR-146a-5p; non-small cell lung cancer; tumor suppressor gene