title: MARCH5 RNA promotes autophagy, migration, and invasion of ovarian cancer cells.
abstract: MARCH5 is a crucial regulator of mitochondrial fission. However, the expression and function of MARCH5 in ovarian cancer have not been determined. This study investigated the expression and function of MARCH5 in ovarian cancer with respect to its potential role in the tumorigenesis of the disease as well as its usefulness as an early diagnostic marker. We found that the expression of MARCH5 was substantially upregulated in ovarian cancer tissue in comparison with the normal control. Silencing MARCH5 in SKOV3 cells decreased TGFB1-induced cell macroautophagy/autophagy, migration, and invasion in vitro and in vivo, whereas the ectopic expression of MARCH5 in A2780 cells had the opposite effect. Mechanistic investigations revealed that MARCH5 RNA may function as a competing endogenous RNA (ceRNA) to regulate the expression of SMAD2 and ATG5 by competing for MIR30A. Knocking down SMAD2 or ATG5 can block the effect of MARCH5 in A2780 cells. Also, silencing the expression of MARCH5 in SKOV3 cells can inhibit the TGFB1-SMAD2/3 pathway. In contrast, the ectopic expression of MARCH5 in A2780 cells can activate the TGFB1-SMAD2/3 pathway. In turn, the TGFB1-SMAD2/3 pathway can regulate MARCH5 and ATG5 through MIR30A. Overall, the results of this study identified MARCH5 as a candidate oncogene in ovarian cancer and a potential target for ovarian cancer therapy.
authors.affiliation: a Department of Obstetrics and Gynecology, Second Affiliated Hospital , Chongqing Medical University , Chongqing , China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Hu
authors.affiliation: a Department of Obstetrics and Gynecology, Second Affiliated Hospital , Chongqing Medical University , Chongqing , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Meng
authors.affiliation: b Department of Anesthesiology , the First Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Zhanqin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: c Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric-Disorders and Department of Pharmacology , College of Pharmaceutical Sciences, Soochow University , Suzhou , Jiangsu , China.
authors.forename: Qiuting
authors.initials: Q
authors.lastname: Yan
authors.affiliation: a Department of Obstetrics and Gynecology, Second Affiliated Hospital , Chongqing Medical University , Chongqing , China.
authors.forename: Xingwei
authors.initials: X
authors.lastname: Jiang
authors.affiliation: d Department of Laboratory Medicine , Chongqing Cancer Institute , Chongqing , China.
authors.forename: Zilan
authors.initials: Z
authors.lastname: Lv
authors.affiliation: a Department of Obstetrics and Gynecology, Second Affiliated Hospital , Chongqing Medical University , Chongqing , China.
authors.forename: Lina
authors.initials: L
authors.lastname: Hu
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D000071187:Autophagy-Related Protein 5 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000071187:Autophagy-Related Protein 5; C546086:MIRN30b microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C515578:MARCHF5 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: ATG5; MARCH5; SMAD2/3; autophagy; invasion; ovarian cancer