Abstract
BackgroundEmerging evidence has noted the important participation of microRNAs (miRNAs) in several human diseases including cancer. This research was launched to probe the function of miR-381 in bladder cancer (BCa) progression.MethodsTwenty-eight patients with primary BCa were included in this study. Cancer tissues and the adjacent normal tissues were obtained. Aberrantly expressed miRNAs in BCa tissues were analyzed using miRNA microarrays. miR-381 expression in the bladder and paired tumor tissues, and in BCa and normal cell lines was determined. The target relationship between miR-381 and BMI1 was predicted online and validated through a luciferase assay. Gain-of-functions of miR-381 and BMI1 were performed to identify their functions on BCa cell behaviors as well as tumor growth in vivo. The involvement of the Rho/ROCK signaling was identified.ResultsmiR-381 was poor regulated in BCa tissues and cells (all p < 0.05). A higher miR-381 level indicated a better prognosis of patients with BCa. Artificial up-regulation of miR-381 inhibited proliferation, invasion, migration, resistance to apoptosis, and tumor formation ability of BCa T24 and RT4 cells (all p < 0.05). miR-381 was found to directly bind to BMI1 and was negatively correlated with BMI1 expression. Overexpression of BMI1 partially blocked the tumor suppressing roles of miR-381 in cell malignancy and tumor growth (all p < 0.05). In addition, miR-381 led to decreased RhoA phosphorylation and ROCK2 activation, which were also reversed by BMI1 (all p < 0.05). Artificial inhibition of the Rho/ROCK signaling blocked the functions of BMI1 in cell growth and metastasis (all p < 0.05).ConclusionThe study evidenced that miR-381 may act as a beneficiary biomarker in BCa patients. Up-regulation of miR-381 suppresses BCa development both in vivo and in vitro through BMI1 down-regulation and the Rho/ROCK inactivation.
Highlights
Emerging evidence has noted the important participation of microRNAs in several human diseases including cancer
Tumor recurrence is a major challenge in bladder cancer (BCa) treatment with a rate of 61% in the first year, and approximately 3–15% recurrent NMIBC may progress to the invasive type MIBC when obtaining additional genetic mutations [4]
The Reverse transcription quantitative polymerase chain reaction (RT-qPCR) results validated that miR-381 was significantly poorly expressed in the tumor tissues in all the included BCa patients (Fig. 1b)
Summary
Emerging evidence has noted the important participation of microRNAs (miRNAs) in several human diseases including cancer. This research was launched to probe the function of miR-381 in bladder cancer (BCa) progression. 81,400 estimated cases in 2020 in the United States alone according to the up-to-date Cancer Statistics [1]. BCa is allocated to two important branches according to the disease states, which are nonmuscle invasive BCa (NMIBC, < T2 stage) and the more risky and metastatic type, muscle invasive BCa (MIBC, Chen et al BMC Urol (2021) 21:5. Tumor recurrence is a major challenge in BCa treatment with a rate of 61% in the first year, and approximately 3–15% recurrent NMIBC may progress to the invasive type MIBC when obtaining additional genetic mutations [4]. The current treatment for BCa is far below expectations, with the survival rate of patients seeing little improvement during the last decades [2]. Identifying more molecular mechanisms may help develop novel effective treatments for this disease
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