In:
Cancer Medicine, Wiley, Vol. 9, No. 2 ( 2020-01), p. 724-736
Abstract:
LncRNAs have been shown to play essential roles in bladder cancer ( BC ) progress. Our microarrays of clinical samples firstly screened that lnc RNA muscleblind‐like 1 antisense RNA 1 ( MBNL 1‐ AS 1) was poorly expressed in BC tissues. However, its biological function in BC remains not well understood. Here we examined the clinical correlations with MBNL 1‐ AS 1 in BC patients. Then, 5673 and T24 cell lines were employed to investigate the role of MBNL1‐AS1 in the proliferation and apoptosis of BC cells in vitro and in vivo. Furthermore, miR‐135a‐5p (miR‐135a)/ PHLPP 2/ FOXO 1 axis was focused to explore its regulatory mechanism in BC . The results showed that MBNL 1‐ AS 1 was significantly downregulated in bladder tumor tissues, and associated with BC progression. In vitro, MBNL 1‐ AS 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 BC cells. The apoptotic cells and the cleavages of caspase‐3/9 were reduced in MBNL 1‐ AS 1‐silenced BC cells. Overexpression of MBNL 1‐ AS 1 had opposite effects on BC cell proliferation and apoptosis. Moreover miR‐135a was demonstrated to interact with MBNL 1‐ AS 1, and inhibiting miR‐135a reversed the effects of shMBNL1‐AS1 on BC cells. The downstream effectors ( PHLPP 2 and FOXO 1) were positively regulated by MBNL 1‐ AS 1, but negatively regulated by miR‐135a. Similar results were also observed in xenograft tumors. In conclusion, this study firstly suggests that MBNL 1‐ AS 1 acts as a tumor suppressor of BC by targeting miR‐135a/ PHLPP 2/ FOXO 1 axis, providing a novel insight for BC diagnosis and treatment.
Type of Medium:
Online Resource
ISSN:
2045-7634
,
2045-7634
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2659751-2
