LncRNA MBNL1‐AS1 represses cell proliferation and enhances cell apoptosis via targeting miR‐135a‐5p/PHLPP2/FOXO1 axis in bladder cancer

摘要

LncRNAs have been shown to play essential roles in bladder cancer ( ) progress. Our microarrays of clinical samples firstly screened that lnc muscleblind‐like 1 antisense 1 ( 1‐ 1) was poorly expressed in BC tissues. However, its biological function in BC remains not well understood. Here we examined the clinical correlations with 1‐ 1 in patients. Then, 5673 and T24 cell lines were employed to investigate the role of MBNL1‐AS1 in the proliferation and apoptosis of cells in vitro and in vivo. Furthermore, miR‐135a‐5p (miR‐135a)/ 2/ 1 axis was focused to explore its regulatory mechanism in . The results showed that 1‐ 1 was significantly downregulated in bladder tumor tissues, and associated with progression. In vitro, 1‐ 1 knockdown increased the number of viable cells and bromodeoxyuridine‐positive cells, accelerated cell cycle, and dysregulated proliferative regulators (Ki67, p21, p27, and Cyclin D1) in cells. The apoptotic cells and the cleavages of caspase‐3/9 were reduced in 1‐ 1‐silenced cells. Overexpression of 1‐ 1 had opposite effects on cell proliferation and apoptosis. Moreover miR‐135a was demonstrated to interact with 1‐ 1, and inhibiting miR‐135a reversed the effects of shMBNL1‐AS1 on cells. The downstream effectors ( 2 and 1) were positively regulated by 1‐ 1, but negatively regulated by miR‐135a. Similar results were also observed in xenograft tumors. In conclusion, this study firstly suggests that 1‐ 1 acts as a tumor suppressor of by targeting miR‐135a/ 2/ 1 axis, providing a novel insight for diagnosis and treatment.