Transcription Factor Induces the Up-regulation of LncRNA to Promote Progression and Adriamycin Resistance in Urothelial Carcinoma of the Bladder

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2019 Jul 17

PMID 31308746

Citations 19

Authors

Zhulei Sun

Gui Huang

Hepeng Cheng

Affiliations

Soon will be listed here.

Abstract

Background: () has been documented to be implicated in carcinogenesis and chemoresistance in solid tumors. Here, we explored the biological role and regulatory mechanism of in progression and chemoresistance of urothelial carcinoma of the bladder (UCB).

Methods: () () mRNA and expression was determined by quantitative reverse transcription polymerase chain reaction. Western blot was performed to determine the protein levels of Nrf2, p-glycoprotein (p-gp), Ki-67 (Ki67), matrix metalloproteinase (MMP)-2 and MMP-9 and cleaved caspase-3. The effects of either or knockdown on the proliferation, invasion, apoptosis and adriamycin (ADM) resistance of UCB cells were evaluated by CCK-8 assay, transwell invasion assay and flow cytometry analysis. Xenograft tumor assay was carried out to confirm the role of and in ADM resistance of UCB cells in vivo.

Results: and were upregulated in UCB tissues and cell lines. A positive correlation between and expression was discovered in UCB tissues. Moreover, and expression levels were higher in ADM-resistant cells compared with those in parental cells. Furthermore, positively regulated the expression of in UCB cells. Knockdown of either or led to the inhibition of cell proliferation and invasion and promotion of cell apoptosis, accompanying with down-regulation of Ki67, MMP-2 and MMP-9 and up-regulation of cleaved caspase-3. Knockdown of either or enhanced the sensitivity of BIU-87/ADM and T24/ADM cells to ADM, as indicated by decreased expression of p-gp. Besides, knockdown of either or inhibited tumor growth in the absence or presence of ADM in vivo.

Conclusions: induces the up-regulation of to promote progression and ADM resistance in UCB.

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