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NCK1-AS1 promotes NCK1 expression to facilitate tumorigenesis and chemo-resistance in ovarian cancerchang, Hua; Li, Baixue; Zhang, Xue; Meng, Xiangkai
Biochemical and biophysical research communications, 02/2020, Letnik: 522, Številka: 2Journal Article
Long non-coding RNAs (lncRNAs) have been unveiled to play crucial parts in tumorigenesis and chemo-resistance of multiple cancers. Herein, we explored the role of NCK1-AS1 in ovarian cancer (OC). As indicated by TCGA, NCK1-AS1 was markedly upregulated in OC tissues. Besides, we found a dramatic upregulation of NCK1-AS1 in OC cell lines relative to the normal IOSE cells. Interestingly, silencing NCK1-AS1 confined cell proliferation, induced apoptosis and suppressed migration and invasion as well as enhanced DDP sensitivity in OC cells. As for mechanistic investigation, starBase (http://starbase.sysu.edu.cn/) suggested that NCK1-AS1 expression in OC tissues was significantly positively correlated with its adjacent gene, NCK adaptor protein 1 (NCK1). Furtherly, we demonstrated that the cytoplasmic NCK1-AS1 competed with NCK1 mRNA for miR-137 binding to boost NCK1 mRNA expression. Importantly, miR-137 inhibition could only offset the suppression of NCK1-AS1 depletion on NCK1 mRNA level but not the protein level. Moreover, NCK1-AS1 stabilized NCK1 protein by hindering c-Cbl-induced degradation via directly interacting with c-Cbl. Furthermore, NCK1 upregulation reversed the influences of NCK1-AS1 inhibition on the biological behaviors and DDP resistance of OC cells. This study disclosed a NCK1-AS1/NCK1 axis in regulating OC progression and chemo-resistance, opening a new path for treatment and chemo-resistance overcoming in OC. •NCK1-AS1 accelerates cell proliferation, migration and invasion as well as chemo-resistance formation in ovarian cancer.•NCK1-AS1 elevates NCK1 mRNA expression by interacting with miR-137.•NCK1-AS1 prevents NCK1 protein from c-Cbl-mediated degradation through competitively interacting with c-Cbl.•NCK1-AS1 contributes to carcinogenesis and chemo-resistance of ovarian cancer through targeting NCK1.
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