title: mir-30d Regulates multiple genes in the autophagy pathway and impairs autophagy process in human cancer cells.
abstract: In human epithelial cancers, the microRNA (miRNA) mir-30d is amplified with high frequency and serves as a critical oncomir by regulating metastasis, apoptosis, proliferation, and differentiation. Autophagy, a degradation pathway for long-lived protein and organelles, regulates the survival and death of many cell types. Increasing evidence suggests that autophagy plays an important function in epithelial tumor initiation and progression. Using a combined bioinformatics approach, gene set enrichment analysis, and miRNA target prediction, we found that mir-30d might regulate multiple genes in the autophagy pathway including BECN1, BNIP3L, ATG12, ATG5, and ATG2. Our further functional experiments demonstrated that the expression of these core proteins in the autophagy pathway was directly suppressed by mir-30d in cancer cells. Finally, we showed that mir-30d regulated the autophagy process by inhibiting autophagosome formation and LC3B-I conversion to LC3B-II. Taken together, our results provide evidence that the oncomir mir-30d impairs the autophagy process by targeting multiple genes in the autophagy pathway. This result will contribute to understanding the molecular mechanism of mir-30d in tumorigenesis and developing novel cancer therapy strategy.
authors.affiliation: Ovarian Cancer Research Center and Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yang
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhong
authors.forename: Janos L
authors.initials: JL
authors.lastname: Tanyi
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Shen
authors.forename: Congjian
authors.initials: C
authors.lastname: Xu
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Tim M
authors.initials: TM
authors.lastname: Zheng
authors.forename: Angela
authors.initials: A
authors.lastname: DeMichele
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000235:genetics*; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D002352:Carrier Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009369:Neoplasms / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D033921:Vesicular Transport Proteins
chemical_list: C466624:ATG12 protein, human; C572313:ATG2B protein, human; C502778:ATG5 protein, human; D051017:Apoptosis Regulatory Proteins; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; C491997:BECN1 protein, human; C116838:BNIP3L protein, human; D000071186:Beclin-1; D002352:Carrier Proteins; C546086:MIRN30b microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D025521:Tumor Suppressor Proteins; D033921:Vesicular Transport Proteins