Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1.

摘要: Background/Aims: Doxorubicin (DOX) is a widely used chemotherapeutic agent for colorectal cancer (CRC). However, the acquirement of DOX resistance limits its clinical application therapy. Mounting evidence has suggested that aberrantly expressed lncRNAs contribute to drug various tumors. Our study aimed explore role and molecular mechanisms lncRNA X-inactive specific transcript (XIST) in chemoresistance CRC DOX. Methods: The expressions XIST, miR-124, serum glucocorticoid-inducible kinase 1 (SGK1) mRNA DOX-resistant tissues cells were detected by qRT-PCR or western blot analysis. sensitivity was assessed detecting IC50 value DOX, protein levels P-glycoprotein (P-gp) glutathione S-transferase-π (GST-π) apoptosis. interactions between miR-124 SGK1 confirmed luciferase reporter assay, blot. Xenograft tumor assay verify XIST vivo. Results: expression upregulated downregulated cells. Knockdown inhibited cells, as evidenced reduced decreased P-gp GST-π enhanced apoptosis XIST-silenced Additionally, positively regulated interacting with suppression strikingly reversed XIST-knockdown-mediated repression on Moreover, SGK1-depletion-elicited decrease greatly restored overexpression inhibition Furthermore, knockdown anti-tumor effect Conclusion: exerted regulatory function possibly through miR-124/SGK1 axis, shedding new light developing promising therapeutic strategy overcome patients.