LINC01535 Promotes the Development of Osteosarcoma Through Modulating miR-214-3p/KCNC4 Axis
Authors Yao X, Wu L, Gu Z, Li J
Received 27 September 2019
Accepted for publication 9 May 2020
Published 8 July 2020 Volume 2020:12 Pages 5575—5585
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Yong Teng
Xiaoke Yao,1,* Lingna Wu,2,* Zuchao Gu,1 Jianhua Li1
1Department of Orthopedics, Chengdu First People’s Hospital, Chengdu 610041, Sichuan, People’s Republic of China; 2Intensive Care Unit, Chengdu First People’s Hospital, Chengdu, Sichuan, 610041, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Jianhua Li
Department of Orthopedics, Chengdu First People’s Hospital, Chengdu 610041, Sichuan, People’s Republic of China
Background: Osteosarcoma (OS) is the most common primary bone tumor in group of children and adolescents. Increasing studies showed that long non-coding RNAs (lncRNAs) exerted important functions in the development of tumors, including OS. LINC01535 is an lncRNA which has been studied in cervical cancer but not in OS.
Aim of the Study: This study was aimed to explore the biological function and mechanism of LINC01535 in OS.
Methods: LINC01535 expression was detected by qRT-PCR. Colony formation assay, EdU assay and CCK-8 assay were applied to check cell proliferation ability in OS. Flow cytometry analysis was conducted to measure cell apoptosis capacity. Wound healing assay and transwell assay were performed to assess cell migration and invasion. Luciferase reporter assay and RNA pull-down assay were carried out to verify the molecular mechanism.
Results: The high expression of LINC01535 was presented in OS tissues and cell lines compared with adjacent normal tissues and human osteoblasts. Moreover, OS patients with high LINC01535 expression exhibited poor prognosis. Loss-of-function assay revealed that silenced LINC01535 significantly attenuated cell proliferation, migration and invasion, and enhanced cell apoptosis in OS. Through mechanistic exploration, we found that LINC01535 interacted with miR-214-3p, and KCNC4 was validated to be a target gene of miR-214-3p. The levels of KCNC4 mRNA and protein were positively modulated by LINC01535 and reversely mediated by miR-214-3p. Based on rescue experiments, KCNC4 overexpression reserved the suppressive function of silenced LINC01535 on OS cell growth, migration and invasion.
Conclusion: LINC01535, miR-214-3p and KCNC4 constituted an effective axis that exerted a pregnant regulation in OS development, which is a quite meaningful discovery for exploring potential therapeutic methods for OS patients.
Keywords: LINC01535, miR-214-3p, KCNC4, osteosarcoma
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