SMAD3 and FTO are involved in miR-5581-3p-mediated inhibition of cell migration and proliferation in bladder cancer

Abstract

Previous research evidence suggests that microRNAs (miRNAs) play an indispensable role in onset and progression of bladder cancer (BCa). Here, we explored the functions and mechanisms of miR-5581-3p in BCa. miR-5581-3p, as a tumor suppressor in BCa, was detected at a lower expression level in BCa tissue and cells in contrast with the non-malignant bladder tissue and cells. Over-expression of miR-5581-3p remarkably dampened the migration and proliferation of BCa in vitro and in vivo. SMAD3 and FTO were identified as the direct targets of miR-5581-3p by online databases prediction and mRNA-seq, which were further verified. SMAD3 as a star molecule in modulating EMT progress of BCa had been formulated in former studies. Meanwhile, FTO proved as an N6-methyladenosine (m6A) demethylase in decreasing m6A modification was confirmed to regulate the migration and proliferation in BCa. In addition, we conducted rescue experiments and confirmed overexpressing miR-5581-3p partially rescued the effects of the overexpressing SMAD3 and FTO in BCa cells. In conclusion, our studies exhibit that miR-5581-3p is a novel tumor inhibitor of BCa.

The relationship between the network of non-coding RNAs-molecular targets and N6-methyladenosine modification in tumors of urinary system

“…3D ) [ 72 ]. Sun et al [ 73 ] reported that miR-5581-3p can inhibit the migration of BCa cells by targeting FTO (Fig. 3E ).…”

Multiomic characterization, immunological and prognostic potential of SMAD3 in pan-cancer and validation in LIHC

“…RNA methylation-related proteins have become promising targets for cancer therapy (24). Pan-cancer data were retrieved from the UCSC database, and from this dataset, we extracted the expression pro les of the SMAD3 gene along with 44 marker genes related to Class III RNA modi cation (comprising m1A (10), m5C (13), and m6A (21) genes) within each sample. Subsequently, Pearson correlation coe cients were computed to elucidate the associations between SMAD3 and these marker genes within the context of ve distinct immune pathways.…”

“…Subsequent studies unveiled that NK-3-S1KD, a genetically engineered stable Smad3-silenced human NK cell line, effectively curbs cancer progression in xenografted mouse models with human liver cancer and melanoma (9). Elevated SMAD3 expression levels also correlate with the progression and prognosis of various cancers, including bladder urothelial carcinoma (BLCA), colon adenocarcinoma (COAD), prostate adenocarcinoma (PRAD), and cervical carcinoma (CESC) (10)(11)(12)(13)(14). Additionally, numerous drugs have been found to regulate tumor proliferation and metastasis through SMAD3, including CDK4 inhibitors and doxorubicin, which induce breast cancer cell apoptosis via SMAD3.…”

The emerging roles and mechanism of N6-methyladenosine (m6A) modifications in urologic tumours progression

“…Conversely, miRNAs can also affect the FTO process during m 6 A modifications. Sun et al ( Sun et al, 2022 ) reported that miR-5581–3p is a tumour suppressor in BC, and FTO is regarded as a direct downstream target of miR-5581–3p. miR-5581–3p suppressed FTO synthesis and inhibited BC progression and proliferation via the miR-5581–3p/FTO/Matrix metallopeptidase 9 (MMP9) axis.…”