piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity

Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has recently been recognized, studies on the role and functional mechanism of piRNAs in lung adenocarcinoma (LUAD) development and progression are limited. In this study, we identified 10 differently expressed piRNAs in LUAD tissues...

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Main Authors: Yongmei Liu, Yanhan Dong, Xinjia He, Anjing Gong, Jinning Gao, Xiaodan Hao, Shuai Wang, Yuqiao Fan, Zibo Wang, Meng Li, Wenhua Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-06-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.651915/full
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author Yongmei Liu
Yanhan Dong
Xinjia He
Anjing Gong
Jinning Gao
Xiaodan Hao
Shuai Wang
Yuqiao Fan
Zibo Wang
Meng Li
Wenhua Xu
author_facet Yongmei Liu
Yanhan Dong
Xinjia He
Anjing Gong
Jinning Gao
Xiaodan Hao
Shuai Wang
Yuqiao Fan
Zibo Wang
Meng Li
Wenhua Xu
author_sort Yongmei Liu
collection DOAJ
description Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has recently been recognized, studies on the role and functional mechanism of piRNAs in lung adenocarcinoma (LUAD) development and progression are limited. In this study, we identified 10 differently expressed piRNAs in LUAD tissues compared to normal tissues, among which, piR-hsa-211106 expression levels were downregulated in LUAD tissues and cell lines. Furthermore, the effects of piR-hsa-211106 on the malignant phenotypes and chemosensitivity of LUAD cells were detected by gain- and loss-of-function analyses in vitro and in vivo, which showed that piR-hsa-211106 inhibited LUAD cell proliferation, tumor growth, and migration, but promoted apoptosis. Moreover, our finding indicated that piR-hsa-211106 is a potential therapeutic target that synergistically imparts anticancer effects with a chemotherapeutic agent for LUAD-cisplatin. Further mechanistic investigation indicated that piR-hsa-211106 could bind to pyruvate carboxylase (PC) by RNA pull down and RNA immunoprecipitation assays and inhibited PC mRNA and protein expression. Our study demonstrates that piR-hsa-211106 inhibits LUAD progression by hindering the expression and function of PC and enhances chemotherapy sensitivity, suggesting that piR-hsa-211106 is a novel diagnostic and therapeutic target for LUAD.
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spelling doaj.art-9517e44a336e45669dac8da8963ef3182022-12-22T04:05:11ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-06-011110.3389/fonc.2021.651915651915piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy SensitivityYongmei Liu0Yanhan Dong1Xinjia He2Anjing Gong3Jinning Gao4Xiaodan Hao5Shuai Wang6Yuqiao Fan7Zibo Wang8Meng Li9Wenhua Xu10Department of Inspection, The Medical Faculty of Qingdao University, Qingdao, ChinaInstitute of Translational Medicine, Qingdao University, Qingdao, ChinaDepartment of Radiation Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaInstitute of Translational Medicine, Qingdao University, Qingdao, ChinaInstitute of Translational Medicine, Qingdao University, Qingdao, ChinaDepartment of Inspection, The Medical Faculty of Qingdao University, Qingdao, ChinaDepartment of Inspection, The Medical Faculty of Qingdao University, Qingdao, ChinaDepartment of Inspection, The Medical Faculty of Qingdao University, Qingdao, ChinaDepartment of Inspection, The Medical Faculty of Qingdao University, Qingdao, ChinaDepartment of Inspection, The Medical Faculty of Qingdao University, Qingdao, ChinaAlthough the importance of PIWI-interacting RNAs (piRNAs) in cancer has recently been recognized, studies on the role and functional mechanism of piRNAs in lung adenocarcinoma (LUAD) development and progression are limited. In this study, we identified 10 differently expressed piRNAs in LUAD tissues compared to normal tissues, among which, piR-hsa-211106 expression levels were downregulated in LUAD tissues and cell lines. Furthermore, the effects of piR-hsa-211106 on the malignant phenotypes and chemosensitivity of LUAD cells were detected by gain- and loss-of-function analyses in vitro and in vivo, which showed that piR-hsa-211106 inhibited LUAD cell proliferation, tumor growth, and migration, but promoted apoptosis. Moreover, our finding indicated that piR-hsa-211106 is a potential therapeutic target that synergistically imparts anticancer effects with a chemotherapeutic agent for LUAD-cisplatin. Further mechanistic investigation indicated that piR-hsa-211106 could bind to pyruvate carboxylase (PC) by RNA pull down and RNA immunoprecipitation assays and inhibited PC mRNA and protein expression. Our study demonstrates that piR-hsa-211106 inhibits LUAD progression by hindering the expression and function of PC and enhances chemotherapy sensitivity, suggesting that piR-hsa-211106 is a novel diagnostic and therapeutic target for LUAD.https://www.frontiersin.org/articles/10.3389/fonc.2021.651915/fullpiRNAlung adenocarcinomacancernon-coding RNApyruvate carboxylasedrug sensitivity
spellingShingle Yongmei Liu
Yanhan Dong
Xinjia He
Anjing Gong
Jinning Gao
Xiaodan Hao
Shuai Wang
Yuqiao Fan
Zibo Wang
Meng Li
Wenhua Xu
piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity
Frontiers in Oncology
piRNA
lung adenocarcinoma
cancer
non-coding RNA
pyruvate carboxylase
drug sensitivity
title piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity
title_full piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity
title_fullStr piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity
title_full_unstemmed piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity
title_short piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity
title_sort pir hsa 211106 inhibits the progression of lung adenocarcinoma through pyruvate carboxylase and enhances chemotherapy sensitivity
topic piRNA
lung adenocarcinoma
cancer
non-coding RNA
pyruvate carboxylase
drug sensitivity
url https://www.frontiersin.org/articles/10.3389/fonc.2021.651915/full
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