Circular RNA circSHPRH inhibits the malignant behaviors of bladder cancer by regulating the miR-942/BARX2 pathway

Abstract

Bladder cancer (BCa) is one of the most common tumors of the genitourinary system. However, the detailed molecular mechanism of BCa progression is still unclear. Recently, an increasing number of studies have demonstrated that circular RNAs (circRNAs) play a critical role in the tumorigenesis and progression of BCa. In this article, we showed that circSHPRH expression was obviously decreased in BCa tissues, compared with adjacent normal tissues. Moreover, a low circSHPRH level was positively correlated with a high grade, a high pathological stage, lymphatic metastasis and an unfavorable prognosis for BCa patients. Cell function studies indicated that silencing circSHPRH dramatically increased the proliferation, migration and invasion of BCa cells. Animal experiments revealed that circSHPRH overexpression repressed tumor growth. Mechanistic studies demonstrated that circSHPRH could combine with miR-942 and serve as a sponge of miR-942, which targets BARX2 in BCa cells. Rescue experiments showed that suppression of miR-942 or BARX2 overexpression could significantly abrogate the promoting effects of circSHPRH silencing on BCa cell proliferation and invasion. Furthermore, circSHPRH overexpression partly eliminated the suppressive effects of miR-942 on BARX2 expression. In addition, circSHPRH knockdown promoted activation of the Wnt/β-catenin signaling pathway by regulating BARX2. Taken together, our findings indicate that circSHPRH serves as a sponge of miR-942 to inhibit BCa progression by upregulating BARX2 expression, thereby inhibiting the Wnt/β-catenin signaling pathway.

CircITGA7 regulates malignant phenotypes in bladder cancer cells via targeting miR‐330‐3p/KLF10 axis

“…For instance, a recent study found that circSETD3 was significantly downregulated in BCa tissues and was associated with tumor size, pathological staging, lymphatic metastasis, and unfavorable prognosis 27 . In another study, circSHPRH was downregulated in BCa tissues and cell lines and lower circSHPRH expression was associated with tumor grade, pathological stage, lymphatic metastasis and unfavorable prognosis 28 . Another BCa‐related circRNA, circSOBP was found to be reduced in BCa tissues and cell lines, and circSOBP overexpression inhibited proliferation, migration, and invasion in vitro and tumorigenesis in vivo 29 .…”

“…27 In another study, circSHPRH was downregulated in BCa tissues and cell lines and lower circSHPRH expression was associated with tumor grade, pathological stage, lymphatic metastasis and unfavorable prognosis. 28 Another BCa-related circRNA, circSOBP was found to be reduced in BCa tissues and cell lines, and circSOBP overexpression inhibited proliferation, migration, and invasion in vitro and tumorigenesis in vivo. 29 Due to the biological stability of circRNA, it is expected to be a novel marker for tumor diagnosis and a therapeutic target.…”

Pancancer analysis of oncogenic BARX2 identifying its prognostic value and immunological function in liver hepatocellular carcinoma

“…In this study, the clinical significance and role of BARX2 in LIHC were first investigated by bioinformatic analysis, and the role and mechanism of BARX2 in LIHC occurrence were predicted by enrichment analysis 14 , 26 , 37 , 38 . However, its specific mechanism of action and clinical application need to be further validated.…”

Pan-cancer analysis of oncogenic BARX2 identifying its prognostic value and immunological function in Liver hepatocellular carcinoma

“…However, the exact mechanism has not been elucidated. Numerous studies have shown that DNA methylation has an impact on the prognosis of different cancers [56,57]. The effect of high BARX2 expression on poor OS may be due to gene body hypermethylation, and hypermethylation of BARX2 in the gene body region is correlated with poor OS in LIHC patients.…”