LncRNA MST1P2/miR‐133b axis affects the chemoresistance of bladder cancer to cisplatin‐based therapy via Sirt1/p53 signaling

Abstract

Although bladder cancer is commonly chemosensitive to standard first-line therapy, the acquisition of the resistance to cisplatin (DDP)-based therapeutic regimens remains a huge challenge. Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and microRNAs, have been reported to play a critical role in cancer resistance to DDP.Here, we attempted to provide a novel mechanism by which the resistance of bladder cancer to DDP treatment could be modulated from the perspective of ncRNA regulation.We demonstrated that lncRNA MST1P2 (lnc-MST1P2) expression was dramatically upregulated, whereas miR-133b expression was downregulated in DDP-resistant bladder cancer cell lines, SW 780/DDP and RT4/DDP. Lnc-MST1P2 and miR-133b negatively regulated each other via targeting miR-133b. Both lnc-MST1P2 silence and miR-133b overexpression could resensitize DDP-resistant bladder cancer cells to DDP treatment. More important, miR-133b could directly target the Sirt1 3′-untranslated region to inhibit its expression. Inc-MST1P2/miR-133b axis affected the resistance of bladder cancer cells to DDP via Sirt1/p53 signaling. In conclusion, MST1P2 serves as a competing endogenous RNA for miR-133b to counteract miR-133b-induced suppression on Sirt1, therefore enhancing the resistance of bladder cancer cells to DDP. MST1P2/miR-133b axis affects the resistance of bladder cancer cells to DDP via downstream Sirt1/p53 signaling. K E Y W O R D S bladder cancer, chemoresistance, cisplatin, miR-133b, MST1P2, Sirt1/p53 signaling

<p>Aloperine Exerts Antitumor Effects on Bladder Cancer in vitro</p>

“…Histological epithelial neoplasms account for 95% of this disease, among which more than 90% are transitional epithelial cell carcinomas. 24,25 The EJ cell line is derived from malignant BC and is progressing to the muscle layer of the bladder wall, in contrast to cell lines derived from non-muscle-infiltrating BC, an early form of BC. At present, different treatment methods are available for BC depending on the pathological stage and grade.…”

lncRNA and Mechanisms of Drug Resistance in Cancers of the Genitourinary System

“…MST1P2 was reported to be significantly upregulated in cisplatin-resistant BC cell lines where it serves as a ceRNA. Indeed, MST1P2 sponges miR-133b, where the expression level was downregulated in the same cell lines [27]. Interestingly, the participation of miR-133b in the regulation of chemoresistance was already described in ovarian cancer [118], colorectal cancer [119], and osteosarcoma [120].…”

“…Interestingly, the participation of miR-133b in the regulation of chemoresistance was already described in ovarian cancer [118], colorectal cancer [119], and osteosarcoma [120]. Among direct targets of this short RNA is oncogene Sirt1 (Sirtuin 1) which was proposed as a possible effector of MST1P2/miR-133b mediated drug resistance [27]. Sirt1 overexpression can inactivate p53, which results in a low response of cancer cells with unmutated p53 to DNA-damaging chemotherapeutics [121] and thus inhibition of cancer cells apoptosis (Figure 2).…”

Non coding RNAs as the critical factors in chemo resistance of bladder tumor cells

“…MiR-133b directly suppressed the SIRT1 expression. MST1P2/miR-133b axis had an important role in cisplatin-resistance of BCa through SIRT1/p53 pathway [17]. It has been shown that there was overexpression of HIF1A-AS2 in tissues and cell lines of BCa following the cisplatin treatment which makes bladder tumor cells resistance to cisplatin-triggered cell death.…”