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MiR-99a suppresses cell invasion and metastasis in nasopharyngeal carcinoma through targeting HOXA1

Authors Wang J, Tang W, Liao M, Liu Y, Ai X

Received 5 November 2016

Accepted for publication 15 December 2016

Published 10 February 2017 Volume 2017:10 Pages 753—761

DOI https://doi.org/10.2147/OTT.S126781

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Chiung-Kuei Huang

Jian-Gang Wang,1,2 Wu-Ping Tang,2 Ming-Chu Liao,1 Yan-Ping Liu,1 Xiao-Hong Ai1

1Department of Radiation Oncology, The First Affiliated Hospital of University of South China, Hengyang, 2Department of Oncology, Shaoyang Hospital of TCM, Shaoyang, People’s Republic of China


Background: Recent studies reported that miRNAs play important roles in the carcinogenesis and progression of nasopharyngeal carcinoma (NPC). Therefore, further studies are warranted to better elucidate the function and mechanism of miRNAs in NPC.
Methods: Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the miR-99a expression in NPC cell lines and tissue samples. Wound healing, transwell migration and invasion, and lung metastatic colonization assays were performed to determine NPC cell migratory, invasive and metastatic abilities of NPC cells. Luciferase reporter assays, quantitative RT-PCR and Western blotting were used to validate the target of miR-99a.
Results: We found that miR-99a was significantly downregulated in NPC cell lines and tissue samples. Ectopic overexpression of miR-99a significantly inhibited NPC cell migration and invasion in vitro, and suppressed lung macroscopic and microscopic metastatic colonization in vivo. Conversely, silencing of miR-99a significantly promoted the migratory and invasive abilities of NPC cells. Furthermore, HOXA1 was validated as a direct target of miR-99a, and ectopic expression of HOXA1 could rescue the suppressive effect of miR-99a overexpression on NPC cell migration and invasion.
Conclusion: Together, these results indicated that miR-99a could inhibit NPC invasion and metastasis by targeting HOXA1, thus providing a novel potential target for miRNA-based treatment for NPC patients in the future.

Keywords: miR-99a, homeobox A1, nasopharyngeal carcinoma, invasion, metastasis

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