MiR4673 improves fitness profile of neoplastic cells by induction of autophagy.

ABSTRACT: Therapeutic resistance of neoplasms is mainly attributed to gradual evolution of mutational profile¹. Here, we demonstrate a microRNA-mediated mechanism that effectively improves fitness of SKBR3 mammary carcinoma cells by cytoplasmic reprogramming. The reprogramming is triggered by endogenous miR4673 transcribed from notch-1 locus. The miRNA downregulates cdk-18, a cyclin-dependent kinase that regulates M-G1 transition in cycling cells^2,3. Suppression of cdk-18 triggers mitophagy and autophagy. Due to high autophagic flux, oestrogen receptor-1⁺/progesterone receptor⁺/p53⁺ (Esr1⁺/Pr⁺/p53⁺) SKBR3 cells are coerced into an Esr1^-/Pr^low/p53^-profile. Increased mitophagy in co

SUBMITTER: Dokumcu K 

PROVIDER: S-EPMC6195512 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature