OncoTargets and Therapy (Jan 2020)
miR-100 Inhibits Cell Growth and Proliferation by Targeting HOXA1 in Nasopharyngeal Carcinoma
Abstract
Weifeng He, 1,* Yun Huang, 2,* Cheng chuan Jiang, 1 Yuan Zhu, 3 Ling Wang, 4 Weiwei Zhang, 1 Weiguo Huang, 2 Ting Zhou, 1, 5 Sanyuan Tang 1 1Department of Oncology, Brain Hospital of Hunan Province, Changsha 410007, Hunan Province, People’s Republic of China; 2Cancer Research Institute, Hengyang Medical College of University of South China, Hengyang 421001, Hunan Province, People’s Republic of China; 3People’s Hospital of Changshou Chongqing, Chongqing 401220, People’s Republic of China; 4Yi Chang Central People’s Hospital, Yichang 443000, Hubei Province, People’s Republic of China; 5Department of Clinical Pharmacy, College of Pharmacy, Hunan University of Traditional Chinese Medicine, Changsha 410007, Hunan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Sanyuan TangDepartment of Oncology, Brain Hospital of Hunan Province, Changsha, Hunan Province, People’s Republic of ChinaTel +86 15273156823Email [email protected] ZhouDepartment of Oncology, Brain Hospital of Hunan Province, Changsha, Hunan Province, People’s Republic of ChinaTel/Fax +86 18374819626Email [email protected]: Increasing evidence indicates that the dysregulation of miRNAs plays a vital role in tumorigenesis and progression of nasopharyngeal carcinoma (NPC). Thus, it is necessary to further investigate the function and mechanism of miRNAs in NPC.Methods: miR-100 expression was analyzed using publicly available databases and then tested using quantitative RT-PCR in NPC tissues and cell lines. MTT and colony formation assays and xenograft tumor model were used to test the NPC cell growth and proliferation abilities while modulating miR-100 expression. The target of miR-100 was predicted with TargetScan and validated with luciferase reporter assay, quantitative RT-PCR, and Western blot.Results: The expression of miR-100 was significantly reduced in NPC tissues and cell lines. Overexpression of miR-100 obviously suppressed NPC cell growth and proliferation, whereas silencing miR-100 promoted NPC cell growth and proliferation in vitro. HOXA1 (homeobox A1) was validated as a direct target of miR-100, and restoring HOXA1 expression could reverse the inhibitive effect of miR-100 on NPC cell growth and proliferation. The mRNA and protein expression of HOXA1 was increased in NPC cell lines. Furthermore, ectopic expression of miR-100 inhibited xenograft tumor growth in vivo.Conclusion: Taken together, our findings suggest that miR-100 could suppress NPC growth and proliferation through targeting HOXA1, providing a novel target for the miRNA-mediated therapy for patients with NPC in the future.Keywords: miR-100, nasopharyngeal carcinoma, proliferation, invasion, HOXA1
