LncRNA Gadd7 Promotes Mitochondrial Membrane Potential Decrease and Apoptosis of Alveolar Type II Epithelial Cells by Positively Regulating MFN1 in an Model of Hyperoxia-induced Acute Lung Injury

Overview

Journal Eur J Histochem

Specialty Biochemistry

Date 2023 May 31

PMID 37254890

Authors

GuoYue Liu

Cunzhi Yin

Mingjiang Qian

Xuan Xiao

Hang Wu

Fujian Fu

Affiliations

Soon will be listed here.

Abstract

The mortality and morbidity rates of ovarian cancer (OC) are high, but the underlying mechanisms of OC have not been characterized. In this study, we determined the role of Rho GTPase Activating Protein 30 (ARHGAP30) in OC progression. We measured ARHGAP30 abundance in OC tissue samples and cells using immunohistochemistry (IHC) and RT-qPCR. EdU, transwell, and annexin V/PI apoptosis assays were used to evaluate proliferation, invasiveness, and apoptosis of OC cells, respectively. The results showed that ARHGAP30 was overexpressed in OC tissue samples and cells. Inhibition of ARHGAP30 suppressed growth and metastasis of OC cells, and enhanced apoptosis. Knockdown of ARHGAP30 in OC cells significantly inhibited the PI3K/AKT/mTOR pathway. Treatment with the PI3K/AKT/mTOR pathway inhibitor buparlisib simulated the effects of ARHGAP30 knockdown on growth, invasiveness, and apoptosis of OC cells. Following buparlisib treatment, the expression levels of p-PI3K, p-AKT, and p-mTOR were significantly decreased. Furthermore, buparlisib inhibited the effects of ARHGAP30 upregulation on OC cell growth and invasiveness. In conclusion, ARHGAP30 regulated the PI3K/AKT/mTOR pathway to promote progression of OC.

Citing Articles

A detailed review of pharmacology of MFN1 (mitofusion-1)-mediated mitochondrial dynamics: Implications for cellular health and diseases.

Alghamdi A Saudi Pharm J. 2024; 32(4):102012.

PMID: 38463181 PMC: 10924208. DOI: 10.1016/j.jsps.2024.102012.

LncRNA FAM225B Regulates PDIA4-Mediated Ovarian Cancer Cell Invasion and Migration via Modulating Transcription Factor DDX17.

Yao C, Zeng L, Liu Q, Qiu X, Chen C Breast J. 2023; 2023:3970444.

PMID: 37720188 PMC: 10501846. DOI: 10.1155/2023/3970444.

References

Zhu X, Lei X, Wang J, Dong W . Protective effects of resveratrol on hyperoxia-induced lung injury in neonatal rats by alleviating apoptosis and ROS production. J Matern Fetal Neonatal Med. 2019; 33(24):4150-4158. DOI: 10.1080/14767058.2019.1597846. View

Zou D, Zhou S, Li L, Zhou J, Tang Z, Wang S . Knockdown of Long Noncoding RNAs of Maternally Expressed 3 Alleviates Hyperoxia-Induced Lung Injury via Inhibiting Thioredoxin-Interacting Protein-Mediated Pyroptosis by Binding to miR-18a. Am J Pathol. 2020; 190(5):994-1005. DOI: 10.1016/j.ajpath.2019.12.013. View

Lu X, Wang C, Wu D, Zhang C, Xiao C, Xu F . Quantitative proteomics reveals the mechanisms of hydrogen-conferred protection against hyperoxia-induced injury in type II alveolar epithelial cells. Exp Lung Res. 2019; 44(10):464-475. DOI: 10.1080/01902148.2019.1601296. View

Jiang J, Wang J, Li C, Mo L, Huang D . Hyperoxia induces alveolar epithelial cell apoptosis by regulating mitochondrial function through small mothers against decapentaplegic 3 (SMAD3) and extracellular signal-regulated kinase 1/2 (ERK1/2). Bioengineered. 2021; 13(1):242-252. PMC: 8805928. DOI: 10.1080/21655979.2021.2012953. View

Zhao J, Ma W, Zhong Y, Deng H, Zhou B, Wu Y . Transcriptional Inhibition of lncRNA gadd7 by CRISPR/dCas9-KRAB Protects Spermatocyte Viability. Front Mol Biosci. 2021; 8:652392. PMC: 7991575. DOI: 10.3389/fmolb.2021.652392. View

Chung K, Hsu C, Fan L, Huang Z, Bhatia D, Chen Y . Mitofusins regulate lipid metabolism to mediate the development of lung fibrosis. Nat Commun. 2019; 10(1):3390. PMC: 6662701. DOI: 10.1038/s41467-019-11327-1. View

Zaib S, Hayyat A, Ali N, Gul A, Naveed M, Khan I . Role of Mitochondrial Membrane Potential and Lactate Dehydrogenase A in Apoptosis. Anticancer Agents Med Chem. 2021; 22(11):2048-2062. DOI: 10.2174/1871520621666211126090906. View

Mei M, Nie J, Sun H, Wang H, Rong L . LncRNA-NEF regulated the hyperoxia-induced injury of lung epithelial cells by FOXA2. Am J Transl Res. 2020; 12(9):5563-5574. PMC: 7540126. View

Zhu Y, Ju H, Lu H, Tang W, Lu J, Wang Q . The function role of ubiquitin proteasome pathway in the ER stress-induced AECII apoptosis during hyperoxia exposure. BMC Pulm Med. 2021; 21(1):379. PMC: 8607682. DOI: 10.1186/s12890-021-01751-9. View

10.

Patil S, Hernandez-Cuervo H, Fukumoto J, Krishnamurthy S, Lin M, Alleyn M . Alda-1 Attenuates Hyperoxia-Induced Acute Lung Injury in Mice. Front Pharmacol. 2021; 11:597942. PMC: 7883597. DOI: 10.3389/fphar.2020.597942. View

11.

Jacobs S, Krishnan J, Lederer D, Ghazipura M, Hossain T, Tan A . Home Oxygen Therapy for Adults with Chronic Lung Disease. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020; 202(10):e121-e141. PMC: 7667898. DOI: 10.1164/rccm.202009-3608ST. View

12.

Qin S, Wang H, Liu G, Mei H, Chen M . miR‑21‑5p ameliorates hyperoxic acute lung injury and decreases apoptosis of AEC II cells via PTEN/AKT signaling in rats. Mol Med Rep. 2019; 20(6):4953-4962. PMC: 6854583. DOI: 10.3892/mmr.2019.10779. View

13.

Wu Y, Zhang Z, Li J, Zhong H, Yuan R, Deng Z . Mechanism of Adipose-Derived Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying miR-21-5p in Hyperoxia-Induced Lung Injury. Stem Cell Rev Rep. 2021; 18(3):1007-1024. DOI: 10.1007/s12015-021-10311-x. View

14.

Liu X, Li D, Zhang W, Guo M, Zhan Q . Long non-coding RNA gadd7 interacts with TDP-43 and regulates Cdk6 mRNA decay. EMBO J. 2012; 31(23):4415-27. PMC: 3512391. DOI: 10.1038/emboj.2012.292. View

15.

Rovira-Llopis S, Banuls C, Diaz-Morales N, Hernandez-Mijares A, Rocha M, Victor V . Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications. Redox Biol. 2017; 11:637-645. PMC: 5284490. DOI: 10.1016/j.redox.2017.01.013. View

16.

Mu G, Deng Y, Lu Z, Li X, Chen Y . miR-20b suppresses mitochondrial dysfunction-mediated apoptosis to alleviate hyperoxia-induced acute lung injury by directly targeting MFN1 and MFN2. Acta Biochim Biophys Sin (Shanghai). 2020; 53(2):220-228. DOI: 10.1093/abbs/gmaa161. View

17.

Zhao J, Li H, Deng H, Zhu L, Zhou B, Yang M . LncRNA gadd7, increased in varicocele patients, suppresses cell proliferation and promotes cell apoptosis. Oncotarget. 2018; 9(4):5105-5110. PMC: 5797036. DOI: 10.18632/oncotarget.23696. View

18.

Wenger H, Cifu A, Lee C . Home Oxygen Therapy for Adults With Chronic Obstructive Pulmonary Disease or Interstitial Lung Disease. JAMA. 2021; 326(17):1738-1739. DOI: 10.1001/jama.2021.12073. View

19.

Chen H, Detmer S, Ewald A, Griffin E, Fraser S, Chan D . Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol. 2003; 160(2):189-200. PMC: 2172648. DOI: 10.1083/jcb.200211046. View

20.

Ratner V, Starkov A, Matsiukevich D, Polin R, Ten V . Mitochondrial dysfunction contributes to alveolar developmental arrest in hyperoxia-exposed mice. Am J Respir Cell Mol Biol. 2009; 40(5):511-8. PMC: 3269235. DOI: 10.1165/rcmb.2008-0341RC. View