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Long Non-Coding RNA HOXA11-AS Modulates Proliferation, Apoptosis, Metastasis and EMT in Cutaneous Melanoma Cells Partly via miR-152-3p/ITGA9 Axis

Authors Xu Y, Zhang J, Zhang Q, Xu H, Liu L

Received 14 September 2020

Accepted for publication 28 December 2020

Published 2 February 2021 Volume 2021:13 Pages 925—939

DOI https://doi.org/10.2147/CMAR.S281920

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Yongfei Xu,1,2 Jianwen Zhang,1 Qiangqiang Zhang,3 Hangxing Xu,4 Linbo Liu1

1Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan, People’s Republic of China; 2Department of Plastic Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang City, Henan, People’s Republic of China; 3Burn Plastic Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang City, Henan, People’s Republic of China; 4Department of Surgery, Luoyang Central Tunnel Hospital, Luoyang City, Henan, People’s Republic of China

Correspondence: Linbo Liu
Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Jinshui District, Zhengzhou, 450000, Henan, People’s Republic of China
Tel +86-13937196215
Email pingtengfut8s@126.com

Background: Long non-coding RNA homeobox A11 antisense RNA (HOXA11-AS) was showed to participate in the progression of different kinds of tumors, but the specific role of HOXA11-AS in cutaneous melanoma is not entirely unambiguous.
Methods: The levels of HOXA11-AS, microRNA-152-3p (miR-152-3p) and integrin alpha9 (ITGA9) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was detected via 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT), and apoptosis was measured by flow cytometry. The assessment of cell metastasis was performed by transwell migration and invasion assays. The protein levels were detected through Western blot. Dual-luciferase reporter assay was utilized to explore the target relationship among HOXA11-AS, miR-152-3p and ITGA9. The effect of HOXA11-AS on melanoma in vivo was investigated via xenograft experiment.
Results: HOXA11-AS and ITGA9 were up-regulated while miR-152-3p was down-regulated in melanoma. Knockdown of HOXA11-AS refrained cell proliferation, metastasis and epithelial–mesenchymal transition (EMT) but induced apoptosis in melanoma cells. HOXA11-AS targeted miR-152-3p and overexpression of HOXA11-AS mitigated the miR-152-3p-induced effects on melanoma cellular behaviors. ITGA9 was a target of miR-152-3p and miR-152-3p inhibitor relieved the repression on proliferation, metastasis and EMT while elevation on apoptosis caused by si-ITGA9 via elevating ITGA9. HOXA11-AS knockdown restrained ITGA9 expression via up-regulating miR-152-3p. Suppression of HOXA11-AS inhibited melanoma progression in part through increasing miR-152-3p and decreasing ITGA9 expression in vivo.
Conclusion: HOXA11-AS modulated proliferation, apoptosis, metastasis and EMT in melanoma cells by regulating miR-152-3p/ITGA9 axis in part. HOXA11-AS could promote melanoma development and be used as a promising biomarker in the diagnosis and treatment for cutaneous melanoma.

Keywords: melanoma, HOXA11-AS, miR-152-3p, ITGA9

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