title: Inhibition of microtubule-associated protein 1 light chain 3B via small-interfering RNA or 3-methyladenine impairs hypoxia-induced HO8910PM and HO8910 epithelial ovarian cancer cell migration and invasion and is associated with RhoA and alterations of the actin cytoskeleton.
abstract: Expression of microtubule‑associated protein 1 light chain 3 (LC3) is correlated with poor prognosis in many human cancers. Hypoxia induces LC3 expression and is an essential characteristic of epithelial ovarian cancer (EOC). The aim of the present study was to elucidate the mechanism by which LC3 facilitates EOC cell migration and invasion under conditions of hypoxia. The effects of LC3B inhibition under hypoxic conditions on migration, invasion, and adhesion in HO8910PM and HO8910 EOC cell lines were investigated. LC3B inhibition was achieved by small‑interfering RNA (siRNA) targeting LC3B or by treatment with 3‑methyladenine (3‑MA). Cell migration, invasion and adhesion and the arrangement of the cytoskeleton were determined by Transwell migration assays and rhodamine phalloidin staining. Western blot analysis was performed to evaluate the expression level of LC3B and the expression and activity of ras homolog gene family member A (RhoA). Increased LC3B expression was associated with HO8910PM and HO8910 cell migration and invasion promoted under hypoxic conditions. LC3B siRNA and 3‑MA treatment each attenuated hypoxia‑induced LC3B expression, along with migration and invasion, and this was associated with a decrease in RhoA expression and disorganization of the actin cytoskeleton. LC3B may promote the migration and invasion of EOC cells by affecting the cytoskeleton via the RhoA pathway. In addition, LC3B may be a marker of tumor hypoxia and/or metastasis in EOC cells.
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Di
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Li
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics*; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D002448:Cell Adhesion / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C066737:RHOA protein, human; C025946:3-methyladenine; D020742:rhoA GTP-Binding Protein; D000225:Adenine