RBM24 exacerbates bladder cancer progression by forming a Runx1t1/TCF4/miR-625-5p feedback loop

Abstract

RNA–binding motif protein 24 (RBM24) acts as a multifunctional determinant of cell fate, proliferation, apoptosis, and differentiation during development by regulating premRNA splicing and mRNA stability. It is also implicated in carcinogenesis, but the functions of RBM24 in bladder cancer (BC) remain unclear. In the present study, we revealed that RBM24 was upregulated in BC tissues. Importantly, we found that a higher level of RBM24 was correlated with poor prognosis in BC patients. Overexpression of RBM24 promoted BC cell proliferation, while depletion of RBM24 inhibited BC cell proliferation in vivo and in vitro. Mechanistically, RBM24 positively regulated Runx1t1 expression in BC cells by binding to and enhancing Runx1t1 mRNA stability. Furthermore, Runx1t1 in turn promoted RBM24 expression by interacting with the transcription factor TCF4 and suppressing the transcription of miR-625-5p, which directly targets RBM24 and suppresses RBM24 expression. RBM24-regulated BC cell proliferation was moderated via the Runx1t1/TCF4/miR-625-5p feedback loop. These results indicate that the RBM24/Runx1t1/TCF4/miR-625-5p positive feedback loop participates in BC progression. Disruption of this pathway may be a potential therapeutic strategy for BC treatment.

E2F6/KDM5C promotes SF3A3 expression and bladder cancer progression through a specific hypomethylated DNA promoter

“…Then, we used the following formula to calculate the tumor volume: tumor volume = (length × width 2)/2. After 28 days, the mice were euthanized by carbon dioxide asphyxiation [ 23 , 25 , 27 ]. The euthanasia protocol is as described previously [ 28 ].…”

“…Morphometry and histology were detected by hematoxylin and eosin staining as described before [ 27 , 29 ]. BC and corresponding normal tissues were fixed in formalin solution and then embedded in conventional paraffin.…”

“…DAPI (157,574; MB Biomedical) was used for nuclear staining. The images were captured using a confocal microscope (DM6000 CFS; Leica) and processed using LAS AF software [ 27 , 29 ].…”

Crucial Roles of miR-625 in Human Cancer

“…In malignant pleural mesothelioma (MPM) (34,35) and thyroid cancer (TC) (36,37), miR-625 was found to be upregulated. It is downregulated in bladder cancer (38), nasopharyngeal carcinoma (NPC) (39), lung cancer (40)(41)(42)(43)(44)(45)(46), HCC (47), cervical cancer (CC) (48,49), osteosarcoma (50), melanoma (51)(52)(53)(54), laryngeal squamous cell carcinoma (LSCC) (55), acute myeloid leukemia (AML) (56), BC (57)(58)(59), glioma (60,61), esophageal cancer (EC) (62)(63)(64), clear cell renal cell carcinoma (65), GC (66)(67)(68)(69)(70), and pancreatic ductal adenocarcinoma (PDAC) (71). In colorectal cancer (CRC), the expression of miR-625 seems to vary, being either high or low.…”

“…In bladder cancer (38), NPC (39), HCC (47), osteosarcoma (50), LSCC (55), ccRCC (65), and PDAC ( 71), miR-625 plays a protective role. Up-regulation of miR-625 can affect tumor progression through different mechanisms of action.…”