Role of microRNA-381 in bladder cancer growth and metastasis with the involvement of BMI1 and the Rho/ROCK axis

Abstract

Background 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. Methods Twenty-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. Results miR-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). Conclusion The 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.

The microRNA-381(miR-381)/Spindlin1(SPIN1) axis contributes to cell proliferation and invasion of colorectal cancer cells by regulating the Wnt/β-catenin pathway

“…For example, dendrobine suppressed the endoplasmic reticulum stress-induced apoptosis by increasing miR-381-3p expression in endothelial cells [ 38 ]. Previously, miR-381 was reported to suppress cell proliferation and metastasis by targeting the BM1 and Rho/ROCK axis in bladder cancer [ 40 ]. Additionally, miR-381 facilitates autophagy and apoptosis by suppressing the RELN-mediated PI3K/Akt pathway in prostate cancer cells [ 41 ].…”

Non-coding RNA and autophagy: Finding novel ways to improve the diagnostic management of bladder cancer

“…The tumor-suppressing properties of miR-381was shown to be blocked by overexpression of BMI. Overexpression of miR-381 decreased RhoA phosphorylation and Rho-associated protein kinase (ROCK2) activation ( Chen et al, 2021a ). miRNA-145 was significantly downregulated in patients with bladder cancer.…”

Identification of Candidate MicroRNA-mRNA Subnetwork for Predicting the Osteosarcoma Progression by Bioinformatics Analysis

“…MicroRNAs (miRNAs) have been proven to be one of the most common endogenous noncoding RNAs, which can bind to the 3′ noncoding sequence of particular messenger RNAs (mRNAs) to modulate their translational performance and stability [ 5 ]. Recently, a good deal of investigations has indicated that abnormal changes of miRNAs partake in the regulation of the occurrence and development of different types of human malignancies and are associated with cell development, cell proliferation, apoptosis, and tumorigenesis [ 6 – 8 ]. Thus, miRNAs are considered to be outstanding biomarkers for the diagnostic analysis, targeting therapy, and prediction of malignant tumors.…”