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Original Article

Korean J Physiol Pharmacol 2023; 27(2): 131-141

Published online March 1, 2023 https://doi.org/10.4196/kjpp.2023.27.2.131

Copyright © Korean J Physiol Pharmacol.

Hsa_circ_0129047 sponges miR-665 to attenuate lung adenocarcinoma progression by upregulating protein tyrosine phosphatase receptor type B

Xiaofan Xia#, Jinxiu Fan#, and Zhongjie Fan*

Department of Respiratory and Critical Care Medicine, Wuhan Red Cross Hospital, Wuhan No.11 Hospital, Wuhan 430015, China

Correspondence to:Zhongjie Fan
E-mail: zhongjiefan9@163.com

#These authors contributed equally to this work.

Author contributions: The tests and data analysis were carried out by X.X. and J.F. The research was created and designed by X.X. Z.F. acquired the data. X.X. and J.F. conducted the interpretation of data. All authors have read and approved this manuscript.

Received: May 10, 2022; Revised: December 26, 2022; Accepted: January 2, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Compelling evidence has demonstrated the critical role of circular RNAs (circRNAs) during lung adenocarcinoma (LUAD) progression. Herein, we explored a novel circRNA, circ_0129047, and detailed its mechanism of action. The expression of circ 0129047, microRNA-665 (miR-665), and protein tyrosine phosphatase receptor type B (PTPRB) in LUAD tissues and cells was determined using reverse transcription quantitative polymerase chain reaction and Western blotting. Cell Counting Kit-8 and colony formation assays were conducted to detect LUAD cell proliferation, and western blotting was performed to quantify apoptosis-related proteins (Bcl-2 and Bax). Luciferase reporter and RNA immunoprecipitation assays were used to validate the predicted interaction between miR-665 and circ_0129047 or PTPRB. A xenograft assay was used for the in vivo experiments. Circ_0129047 and PTPRB were downregulated in LUAD tissues and cells, whereas miR-665 expression was upregulated. Overexpression of circ_0129047 suppresses LUAD growth in vivo and in vitro. Circ_0129047 is the target of miR-665, and the miR-665 mimic ablated the antiproliferative and pro-apoptotic phenotypes of LUAD cells by circ_0129047 augmentation. MiR-665 targets the 3ʹUTR of PTPRB and downregulates PTPRB expression. PTPRB overexpression offsets the pro-proliferative potential of miR-665 in LUAD cells. Circ_0129047 sequestered miR-665 and upregulated PTPRB expression, thereby reducing LUAD progression, suggesting a promising approach for preventing LUAD.

Keywords: Adenocarcinoma, circ_0129047, Lung, miR-665, PTPRB