title: MiR-15a and miR-16 induce autophagy and enhance chemosensitivity of Camptothecin.
abstract: It has been reported that persistent or excessive autophagy promotes cancer cell death during chemotherapy, either by enhancing the induction of apoptosis or mediating autophagic cell death. Here, we show that miR-15a and miR-16 are potent inducers of autophagy. Rictor, a component of mTORC2 complex, is directly targeted by miR-15a/16. Overexpression of miR-15a/16 or depletion of endogenous Rictor attenuates the phosphorylation of mTORC1 and p70S6K, inhibits cell proliferation and G1/S cell cycle transition in human cervical carcinoma HeLa cells. Moreover, miR-15a/16 dramatically enhances anticancer drug camptothecin (CPT)-induced autophagy and apoptotic cell death in HeLa cells. Collectively, these data demonstrate that miR-15a/16 induced autophagy contribute partly to their inhibition of cell proliferation and enhanced chemotherapeutic efficacy of CPT.
authors.affiliation: a School of Life Sciences; Tsinghua University ; Beijing , China.
authors.forename: Nunu
authors.initials: N
authors.lastname: Huang
authors.forename: Jiangbin
authors.initials: J
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Qiu
authors.forename: Qing
authors.initials: Q
authors.lastname: Lyu
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.forename: Weidong
authors.initials: W
authors.lastname: Xie
authors.forename: Naihan
authors.initials: N
authors.lastname: Xu
authors.forename: Yaou
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001343:Autophagy / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D002166:Camptothecin / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D000076226:Rapamycin-Insensitive Companion of mTOR Protein
chemical_list: D020413:3' Untranslated Regions; D000972:Antineoplastic Agents, Phytogenic; D002352:Carrier Proteins; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; C492571:RICTOR protein, human; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D002166:Camptothecin
keywords: BAFA1, bafilomycin A1; CPT, Camptothecin; Camptothecin; LC3, microtubule-associated protein 1 light chain 3; MUT, mutated; NC, negative control.; Rictor; Rictor, Rptor independent companion of mTOR complex 2; UTR, untranslated region; autophagy; cell proliferation; mTOR; mTOR, mechanistic target of rapamycin; miRNA, microRNA; microRNA