Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis

Abstract Background Circular RNAs (circRNAs) are a class of important regulators in various human cancers, including lung cancer. Here, we aimed to investigate the role of circ_0010235 in lung cancer. Methods The expression of circ_0010235, microRNA‐636 (miR‐636) and PDL1 was measured by quantitativ...

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Main Authors: Jixing Zhao, Wu Yan, Wencong Huang, Yongsheng Li
Format: Article
Language:English
Published: Wiley 2022-04-01
Series:Thoracic Cancer
Subjects:
Online Access:https://doi.org/10.1111/1759-7714.14338
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author Jixing Zhao
Wu Yan
Wencong Huang
Yongsheng Li
author_facet Jixing Zhao
Wu Yan
Wencong Huang
Yongsheng Li
author_sort Jixing Zhao
collection DOAJ
description Abstract Background Circular RNAs (circRNAs) are a class of important regulators in various human cancers, including lung cancer. Here, we aimed to investigate the role of circ_0010235 in lung cancer. Methods The expression of circ_0010235, microRNA‐636 (miR‐636) and PDL1 was measured by quantitative real‐time PCR (qRT‐PCR). Cell proliferation was evaluated by CCK‐8, colony formation, and 5‐ethynyl‐2′‐deoxyuridine (EdU) assays. Cell apoptosis was detected by flow cytometry. Cell invasion was assessed by transwell assay. All protein levels were determined by western blot assay. In order to detect the roles of circ_0010235 in immune escape, lung cancer cells were cocultured with peripheral blood mononuclear cells (PBMCs) or cytokine‐induced killer (CIK) cells in vitro. The relationship between miR‐636 and circ_0010235 or PDL1 was verified by dual‐luciferase reporter assay and RNA pulldown assay. Immunohistochemistry (IHC) analysis was used to detect Ki67 and programmed death‐ligand 1 (PDL1) expression. A xenograft tumor model was established to verify the function of circ_0010235 in vivo. Results Circ_0010235 was overexpressed in lung cancer. Circ_0010235 knockdown inhibited proliferation, invasion and immune escape and promoted apoptosis of lung cancer cells. MiR‐636 was a target of circ_0010235, and miR‐636 inhibition reversed the effects of circ_0010235 knockdown in lung cancer cells. PDL1 was a direct target of miR‐636, and miR‐636 suppressed the proliferation and invasion and increased apoptosis and antitumor immunity in lung cancer cells by downregulating PDL1. Moreover, circ_0010235 positively regulated PDL1 expression by sponging miR‐636. Additionally, circ_0010235 knockdown hampered tumorigenesis in vivo. Conclusion Circ_0010235 knockdown inhibited lung cancer progression and increased antitumor immunity by regulating the miR‐636/PDL1 axis.
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spelling doaj.art-5a8a1b095fee42079884913daf61e0932022-12-22T02:50:25ZengWileyThoracic Cancer1759-77061759-77142022-04-0113796597610.1111/1759-7714.14338Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axisJixing Zhao0Wu Yan1Wencong Huang2Yongsheng Li3Department of Thoracic Surgery Huizhou Central People's Hospital Huizhou ChinaDepartment of Thoracic Surgery Huizhou Central People's Hospital Huizhou ChinaDepartment of Thoracic Surgery Huizhou Central People's Hospital Huizhou ChinaDepartment of Thoracic Surgery Huizhou Central People's Hospital Huizhou ChinaAbstract Background Circular RNAs (circRNAs) are a class of important regulators in various human cancers, including lung cancer. Here, we aimed to investigate the role of circ_0010235 in lung cancer. Methods The expression of circ_0010235, microRNA‐636 (miR‐636) and PDL1 was measured by quantitative real‐time PCR (qRT‐PCR). Cell proliferation was evaluated by CCK‐8, colony formation, and 5‐ethynyl‐2′‐deoxyuridine (EdU) assays. Cell apoptosis was detected by flow cytometry. Cell invasion was assessed by transwell assay. All protein levels were determined by western blot assay. In order to detect the roles of circ_0010235 in immune escape, lung cancer cells were cocultured with peripheral blood mononuclear cells (PBMCs) or cytokine‐induced killer (CIK) cells in vitro. The relationship between miR‐636 and circ_0010235 or PDL1 was verified by dual‐luciferase reporter assay and RNA pulldown assay. Immunohistochemistry (IHC) analysis was used to detect Ki67 and programmed death‐ligand 1 (PDL1) expression. A xenograft tumor model was established to verify the function of circ_0010235 in vivo. Results Circ_0010235 was overexpressed in lung cancer. Circ_0010235 knockdown inhibited proliferation, invasion and immune escape and promoted apoptosis of lung cancer cells. MiR‐636 was a target of circ_0010235, and miR‐636 inhibition reversed the effects of circ_0010235 knockdown in lung cancer cells. PDL1 was a direct target of miR‐636, and miR‐636 suppressed the proliferation and invasion and increased apoptosis and antitumor immunity in lung cancer cells by downregulating PDL1. Moreover, circ_0010235 positively regulated PDL1 expression by sponging miR‐636. Additionally, circ_0010235 knockdown hampered tumorigenesis in vivo. Conclusion Circ_0010235 knockdown inhibited lung cancer progression and increased antitumor immunity by regulating the miR‐636/PDL1 axis.https://doi.org/10.1111/1759-7714.14338antitumor immunitycirc_0010235lung cancermiR‐636PDL1
spellingShingle Jixing Zhao
Wu Yan
Wencong Huang
Yongsheng Li
Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis
Thoracic Cancer
antitumor immunity
circ_0010235
lung cancer
miR‐636
PDL1
title Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis
title_full Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis
title_fullStr Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis
title_full_unstemmed Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis
title_short Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis
title_sort circ 0010235 facilitates lung cancer development and immune escape by regulating mir 636 pdl1 axis
topic antitumor immunity
circ_0010235
lung cancer
miR‐636
PDL1
url https://doi.org/10.1111/1759-7714.14338
work_keys_str_mv AT jixingzhao circ0010235facilitateslungcancerdevelopmentandimmuneescapebyregulatingmir636pdl1axis
AT wuyan circ0010235facilitateslungcancerdevelopmentandimmuneescapebyregulatingmir636pdl1axis
AT wenconghuang circ0010235facilitateslungcancerdevelopmentandimmuneescapebyregulatingmir636pdl1axis
AT yongshengli circ0010235facilitateslungcancerdevelopmentandimmuneescapebyregulatingmir636pdl1axis