|Table of Contents|

Overexpression of OMA1 induces apoptosis of lung adenocarcinoma A549 cells by promoting mitochondrial release of cytochrome C

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 08
Page:
1414-1419
Research Field:
Publishing date:

Info

Title:
Overexpression of OMA1 induces apoptosis of lung adenocarcinoma A549 cells by promoting mitochondrial release of cytochrome C
Author(s):
SUN YongpanLONG QianZHOU XiaojiangKONG DemiaoLIU BoLU Zhansheng
Department of Thoracic Surgery,Guizhou Provincial People's Hospital,Guizhou Guiyang 550002,China.
Keywords:
lung adenocarcinomaOMA1cytochrome Ccell apoptosismitochondria
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2023.08.006
Abstract:
Objective:To investigate the expression level of OMA1 in lung adenocarcinoma and its effect on apoptosis of lung adenocarcinoma A549 cells and its mechanism.Methods:The cancerous tissues samples and para-cancerous tissues (≥5 cm from the tumor margin) were collected from 42 patients with pathologically confirmed lung adenocarcinoma stored in our hospital from January 2018 to October 2019.The expression of OMA1 in cancerous tissues and para-cancerous tissues was detected by immunohistochemistry.Human lung adenocarcinoma cell lines NCI-H2009,Calu-3,SPC-A-1,A549 and human normal lung epithelial cells BEAS-2B were cultured in vitro.The expression levels of OMA1 mRNA and protein in cells were detected by qRT-PCR and Western blotting.A549 cells were infected with OMA1 overexpression lentivirus and its no-load lentivirus,which were divided into OMA1 overexpression lentivirus infection group (OMA1 group) and no-load lentivirus infection group (Vector group),and blank control group (Blank group) was set.The cell proliferation activity was detected by MTT.The apoptosis level was detected by flow cytometry.The changes of mitochondrial membrane potential were detected by JC-10 staining.The expression level of OMA1 mRNA was detected by qRT-PCR.Western blotting was used to detect the expression levels of OMA1,cleaved caspase-3,OPA1,and Cyt C protein in mitochondria and cytoplasm of cells.Results:The expression level of OMA1 in cancerous tissues of lung adenocarcinoma patients was significantly lower than that in para-cancerous tissues (P<0.05).The mRNA and protein expression levels of OMA1 in NCI-H2009,Calu-3,SPC-A-1 and A549 cells were significantly lower than those in BEAS-2B cells (P<0.05).Compared with Blank group or Vector group,the mRNA and protein expression levels of OMA1,apoptosis rate,expression levels of cleaved caspase-3 protein and Cyt C protein in cytoplasm of OMA1 group were significantly increased (P<0.05),while the cell proliferation activity,mitochondrial membrane potential,expression levels of OPA1 protein and Cyt C protein in mitochondria were significantly decreased (P<0.05).Conclusion:OMA1 is low expressed in lung adenocarcinoma tissues and cell lines,and overexpression of OMA1 can induce apoptosis of lung adenocarcinoma A549 cells by down-regulating OPA1 protein expression,damaging mitochondrial membrane potential,and accelerating the release of mitochondrial Cyt C.

References:

[1] TORRE LA,SIEGEL RL,JEMAL A.Lung cancer statistics[J].Adv Exp Med Biol,2016,893:1-19.
[2] BOHOVYCH I,DIETZ JV,SWENSON S,et al.Redox regulation of the mitochondrial quality control protease Oma1[J].Antioxid Redox Signal,2019,31(6):429-443.
[3] ALAVI MV.Targeted OMA1 therapies for cancer[J].Int J Cancer,2019,145(9):2330-2341.
[4] DAVEREY A,LEVYTSKYY RM,STANKE KM,et al.Depletion of mitochondrial protease OMA1 alters proliferative properties and promotes metastatic growth of breast cancer cells[J].Sci Rep,2019,9(1):14746.
[5] AMINI MA,KARIMI J,KHODADADI I,et al.Overexpression of ROMO1 and OMA1 are potentially biomarkers and predict unfavorable prognosis in gastric cancer[J].J Gastrointest Cancer,2020,51(3):939-946.
[6] WU Z,ZUO M,ZENG L,et al.OMA1 reprograms metabolism under hypoxia to promote colorectal cancer development[J].EMBO Rep,2021,22(1):e50827.
[7] 王玉环,张淑华,穆淑坤,等.去泛素化酶USP33通过下调SLIT2/ROBO1信号通路抑制肺腺癌的侵袭和转移[J].南方医科大学学报,2018,38(8):956- 961. WANG YH,ZHANG SH,MU SK,et al.USP33 suppresses lung adenocarcinoma lung cell invasion and metastasis by down-regulating SLIT2/ROBO1 signaling pathway[J].Journal of Southern Medical University,2018,38(8):956-961.
[8] HOY H,LYNCH T,BECK M.Surgical treatment of lung cancer[J].Crit Care Nurs Clin North Am,2019,31(3):303-313.
[9] 张福全,段善州,黄秉韬,等.X连锁凋亡抑制蛋白相关因子1对人肺腺癌增殖和诱导其凋亡的作用[J].中华实验外科杂志,2014,31(3):678. ZHANG FQ,DUAN SZ,HUANG BT,et al.Effects of X-linked inhibitor of apoptosis protein related factor 1 on proliferation and apoptosis induction of human lung adenocarcinoma[J].Chinese Journal of Experimental Surgery,2014,31(3):678.
[10] 易亮,孙丹,韩倩,等.多聚肌苷酸-多聚胞苷酸诱导肺腺癌A549细胞凋亡的机制[J].国际肿瘤学杂志,2017,44(5):321-326. YI L,SUN D,HAN Q,et al.Mechanism of Poly(I∶C)-induced apoptosis in lung adenocarcinoma A549 cells[J].Journal of International Oncology,2017,44(5):321-326.
[11] 赵娜,魏素菊,洪雷,等.康莱特注射液对吉非替尼诱导人肺腺癌A549细胞株凋亡影响的实验研究[J].临床肿瘤学杂志,2015,20(1):1-7. ZHAO N,WEI SJ,HONG L,et al.Effects of kanglaite injection on the apoptosis induced by gefitinib in lung adenocarcinoma A549 cell line[J].Chinese Clinical Oncology,2015,20(1):1-7.
[12] 吴佳怡.细胞凋亡研究进展[J].当代化工研究,2018,12:190-192. WU JY.Research progress of cell apoptosis[J].Chenmical Intermediate,2018,12:190-192.
[13] ANAND R,WAI T,BAKER MJ,et al.The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission[J].J Cell Biol,2014,204(6):919-929.
[14] DAVEREY A,LEVYTSKYY RM,STANKE KM,et al.Depletion of mitochondrial protease OMA1 alters proliferative properties and promotes metastatic growth of breast cancer cells[J].Sci Rep,2019,9(1):14746.
[15] OLICHON A,BARICAULT L,GAS N,et al.Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity,leading to cytochrome c release and apoptosis[J].J Biol Chem,2003,278(10):7743-7746.
[16] HOY H,LYNCH T,BECK M.Surgical treatment of lung cancer[J].Crit Care Nurs Clin North Am,2019,31(3):303-313.
[17] FENG X,YU Y,HE S,et al.Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism[J].Cancer Lett,2017,385:12-20.
[18] 王佳,张炯.蛇床子素通过抑制线粒体介导的凋亡信号途径减轻脑缺血再灌注损伤[J].西安交通大学学报(医学版),2017,38(1):131-135. WANG J,ZHANG J.Osthole alleviates cerebral ischemia-reperfusion inj ury by suppressing mitochondrial mediating apoptosis[J].Journal of X'an Jiaotong University (Medical Sciences),2017,38(1):131-135.
[19] YU X,WANG L,ACEHAN D,et al.Three-dimensional structure of a double apoptosome formed by the Drosophila Apaf-1 related killer[J].J Mol Biol,2006,355(3):577-589.

Memo

Memo:
贵州省科技厅科技计划项目(编号:黔科合基础【2019】1202)
Last Update: 1900-01-01