<p>lncRNA KCNQ1OT1 enhances the chemoresistance of oxaliplatin in colon cancer by targeting the miR-34a/ATG4B pathway</p>

Abstract

Purpose The chemoresistance of colon cancer to oxaliplatin (L-OHP) indicates poor prognosis. Long non-coding RNA (lncRNA) KCNQ1OT1 (KCNQ1 opposite strand/antisense transcript 1) has been shown to participate in the tumorigenesis of several types of cancers. However, little is known about the role of KCNQ1OT1 in the chemoresistance and prognosis of colon cancer. Materials and methods Quantitative-PCR and Western blot were used to measure the expression profiles of KCNQ1OT1, miR-34a, and Atg4B in colon cancer tissues and cells. Cell viability assay and flow cytometry were used to examine their effects on cell proliferation and death. Cleavage of LC3 and GFP-LC3 plasmid transfection were used to detect autophagic activity. Double luciferase reporter assay was used to verify the interactions between miRNA and lncRNA or mRNA. Xenograft tumor model was used to verify the effects of KCNQ1OT1 in vivo. Results In this study, it is shown that the expression level of KCNQ1OT1 was increased in tumor, which indicated poor prognosis in colon cancer patients. Using colon cancer cell lines HCT116 and SW480, it was demonstrated that knockdown of KCNQ1OT1 decreased the cell viability and increased the apoptosis rates upon L-OHP treatment. Further studies indicated that Atg4B upregulation was partially responsible for KCNQ1OT1-induced protective autophagy and chemoresistance. Moreover, miR-34a functioned as a bridge between KCNQ1OT1 and Atg4B, which could be sponged by KCNQ1OT1, while it could also bind to the 3′-UTR of Atg4B and downregulate its expressions. Finally, we show that the KCNQ1OT1/miR-34a/Atg4B axis regulated the chemoresistance of colon cancer cells in vitro and in vivo. Conclusion lncRNA KCNQ1OT1 promoted the chemoresistance of colon cancer by sponging miR-34a, thus upregulating the expressions of Atg4B and enhancing protective autophagy. KCNQ1OT1 might become a promising target for colon cancer therapeutics.

<p>LncRNA ASB16-AS1 Promotes Growth And Invasion Of Hepatocellular Carcinoma Through Regulating miR-1827/FZD4 Axis And Activating Wnt/β-Catenin Pathway</p>

“…9,20,21 For example, lncRNA KCNQ1OT1 promotes colon cancer chemoresistance through sponging miR-34a and upregulating ATG4B. 24 LncRNA MALAT1 regulates stemness of colorectal cancer cells by interacting with miR-20b-5p to promote Oct4 expression. 25 In addition, lncRNA DGCR5 inhibits HCC cell proliferation and invasion via sponging miR-346 and activating KLF14.…”

Retracted Article: Long non-coding RNA NEAT1 accelerates cell progression in cervical cancer by regulating the miR-889-3p/E2F7 axis through the activation of the PI3K/AKT pathway

“…Long noncoding RNAs (lncRNAs) are essential gene modulators that participate in cell cycle, metabolism, survival, inammation, metastasis and drug resistance. [7][8][9] Nuclearenriched autosomal transcript 1 (NEAT1) located at 11q13.1 is a newly emerged oncogene that is involved in the tumorigenesis of a variety of cancers. 10 The dysregulation of NEAT1 is implicated in the poor prognosis of many cancers.…”

MicroRNA-935 mediates the regulatory effect of lncRNA KCNQ1OT1 on tumor progression of breast cancer

“…The expression and biological function of KCNQ1OT1 has been investigated in a study by Feng et al, which reported that KCNQ1OT1 expression was elevated in BCa tissues and cells, and the overexpression of KCNQ1OT1 could enhance BCa cell proliferation through the miR-145/CCNE2 pathway (11). In addition, the KCNQ1OT1 has been reported to facilitate the chemoresistance of colon cancer cells (26) and regulate tumor cell proliferation and apoptosis of tongue cancer cells (27). Similarly, our analysis results also detected the upregulated KCNQ1OT1 expression in BCa cells and serum samples, and found the promoting effect of KCNQ1OT1 on BCa cell proliferation, migration and invasion.…”