Long non-coding RNA HAND2-AS1 delays cervical cancer progression via its regulation on the microRNA-21-5p/TIMP3/VEGFA axis
Authors: Wentong Liang
Zhijun Zhang
Ting Zou
Yan Gao
Mingrong Qie
Journal: Cancer Gene Therapy (2021)
Discipline: CLINICAL MEDICINE
Keywords: Cervical cancer; long non-coding RNAs; HAND2-AS1; miR-21-5p; TIMP3
Affiliations: Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, P.R. China., Department of Gynecology, Guizhou Provincial People's Hospital, Guiyang, 550002, P.R. China., Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, 610041, P.R. China., Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, P.R. China. ., Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, 610041, P.R. China. .

Abstract:  Cervical cancer is a common cause of cancer-related mortality in women. Mounting evidence suggests that long non-coding RNAs (lncRNAs) function vitally in many cancers. In this study, we discovered that the regulation of the heart and neural crest derivatives expressed 2-antisense RNA 1 (HAND2-AS1) in cervical cancer. RT-qPCR was conducted to detect the expression of HAND2-AS1 and microRNA-21-5p (miR-21-5p). The relationship of HAND2-AS1 and miR-21-5p was identified by dual-luciferase reporter gene assay. The roles of HAND2-AS1, miR-21-5p and tissue inhibitor of metalloproteinases-3 (TIMP3) in cervical cancer were accessed via gain- and loss-of-function approaches. The expression of related proteins in the vascular endothelial growth factor A (VEGFA) signaling pathway was detected through Western blot analysis. Finally, xenografts of cervical cancer in nude mice were established to assess the effect of HAND2-AS1 on tumorigenesis in vivo. HAND2-AS1 and TIMP3 were downregulated in cervical cancer, which were identified to be associated with a poor prognosis of patients with cervical cancer. Moreover, HAND2-AS1 was upregulated the expression of TIMP3 through competitively binding to miR-21-5p. Overexpressed HAND2-AS1 or downregulated miR-21-5p inhibited cell proliferation, migration, and invasion while promoting cell apoptosis, in association with increased expression of proteins in VEGFA signaling pathway. These changes were reversed by silencing of TIMP3. Overexpressed HAND2-AS1 reduced the tumor formation ability in nude mice. In summary, HAND2-AS1 may exert inhibitory effects on cervical cancer cell growth and cervical cancer development through its regulation on the miR-21-5p/TIMP3/VEGFA axis. This highlights that HAND2-AS1 may serve as a potential target for cervical cancer diagnosis and treatment. 

Retracted: No

PubPeer comments:
 Figs 4I L, 5E G, 6F. ![file] A surprising number of papers have WBs that sample the same corner of  morphology space , resembling rows of bow-ties on a grainy background. Here, Figs 2E, 3C G I, 4B F, 5A B C H, 6C from [Lin et al (2021)] . ![file] Figs 1D H K, 2F I, 3D H from [Qi et al (2021)] . ![file] Figs 3B D E G K, 4B D F H, 5A G C from [Zhou et al (2020)] . ![file] -------------------------------  ACKNOWLEDGEMENTS We acknowledge and appreciate our colleagues for their valuable suggestions and technical assistance for this study. This specific acknowledgement sentence often appears in the products of papermills. [Dimensions.ai] helpfully provides a graph of its popularity against time. ![file] ,