H19-derived miR-675 contributes to bladder cancer cell proliferation by regulating p53 activation

Abstract

Long noncoding RNA 19 (H19) has been shown to promote bladder cancer cell proliferation and metastasis. However, little is known about how miR-675, mature product of H19, contributes to bladder cancer cell proliferation. In this study, we first evaluated the expression of miR-675 in bladder cancer tissues by quantitative real-time PCR (qRT-PCR) and defined its biological functions by flow cytometry and Western blotting. We found that miR-675 expression levels were remarkably increased in bladder cancer tissues as compared with adjacent noncancerous tissues or normal bladder tissue from health donors; moreover, enhanced miR-675 expression was also observed in bladder cancer cell lines. Ectopic expression of H19 significantly increased bladder cancer cell proliferation and miR-675 expression in vitro. Furthermore, overexpression of miR-675 promoted bladder cancer cell proliferation, while suppression of miR-675 induced G1 phase cell cycle arrest and promoted cell apoptosis. Western blotting analysis further identified that miR-675 inhibited p53 activation, decreased the ratio of Bax/Bcl-2 and cyclin D1 expression in bladder cancer cells; those effects may result in the abnormal proliferation of bladder cancer cells. In conclusion, abnormal enhanced miR-675 expression increases bladder cancer growth by regulating p53 activation, and thus may be helpful in the development of effective treatment strategies for bladder cancer.

Huaier Extract Inhibits Breast Cancer Progression Through a LncRNA-H19/MiR-675-5p Pathway

“…Previous studies demonstrate that H19 exon 1 encodes the precursor for miR-675, which generates two conserved miRNAs (miR-675-5p and miR-675-3p) [27, 29, 35, 36]. Therefore, we explored the possibility that miR-675-5p was associated with the function of H19 in Huaier-mediated tumor suppression.…”

Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

“…Emerging evidence indicates that H19 possesses oncogenic, osteogenic differentiatic and cardiopathy genesis properties and is the key regulator in carcinogenesis, metastasis, cell or tissue differentiation and senescence [25,30,37,38]. Overexpression of H19 promotes cellular proliferation, differentiation and migration in vitro, whereas knockdown of H19 inhibits these effects [24,37,39].…”

“…H19/ miR-675 functions in an indirect way by targeting important downstream genes. Many targets of miR-675 have been identified, such as Twist1 and RB in hepatocellular carcinoma and colorectal cancer [27,28], CaMKIIδ in cardiomyocyte hypertrophy [29], RUNX1 and p53 in bladder cancer [30], and TGF-β1/Smad3 in osteogenic differentiation [37]. We show that CRYAA, which encodes the predominant structural protein involved in the maintenance of lens clarity and refractive properties, is a new target of miR-675 in HLECs and is involved in the pathogenesis of nuclear ARC.…”

“…Many targets of miR-675 have been identified, such as Twist1 and RB in hepatocellular carcinoma and colorectal cancer [27,28]; CaMKIIδ in cardiomyocyte hypertrophy [29]; RUNX1 and p53 in bladder cancer [30]; and TGF-β1/Smad3 in osteogenic differentiation [31]. We thus further investigate the expression level of the above-mentioned target genes between nuclear ARC and transparent lens capsules by qRT-PCR.…”

HMGA1P7-pseudogene regulates H19 and Igf2 expression by a competitive endogenous RNA mechanism

“…In particular, the noncoding H19 has a critical role in genomic imprinting during cell growth and development21. The loss of imprinting results in misexpression of H19 and was detected in many tumors including hepatocellular22, bladder23, gastric2425 and colon26 cancer. IGF2 codes for a mitogenic growth factor that is active in early development and has a critical role in embryonic and fetal growth27.…”