Alteration of miR-21, miR-433 and miR-590 tissue expression related to the TGF-ß signaling pathway in ulcerative colitis patients.

Ulcerative colitis (UC) is an inflammatory disease, and studies have suggested a role for TGF-ß signalling pathway in the pathogenesis of UC. In the present study, we evaluated expression of TGF-ß signalling genes and their regulatory microRNAs in patients with UC and control subjects. The expression of TGF-ß1, SMAD2, SMAD3, miR-21, miR-101, miR-433, and miR-590 were evaluated using real-time PCR in biopsy samples of the patients and controls. Results showed increased expression of TGF-ß1 and SMAD3 in the patients compared to controls. In addition, miR-21 and miR-433 were found to be higher in the patients compared to controls; however, miR-590 was found to be lower. Moreover, miR-433 was demonstrated to have positive correlation with SMAD3 and TGF-ß while miR-21 was positively correlated with TGF-ß1. MiR-590 was negatively correlated with SMAD2 and SMAD3. Results of the present study suggested a role for TGF-ß signalling pathway related microRNAs in pathogenesis of UC.

MicroRNA-30c-2-3p regulates ER stress and induces apoptosis in ovarian cancer cells underlying ER stress.

Ovarian cancer is a common gynecologic cancer with a high rate of recurrence, drug resistance, and mortality, thereby necessitating novel molecular target therapies. Ovarian cancer as a solid tumor has constantly been challenged by endoplasmic reticulum stress (ERS). Currently, XBP1 as a therapeutic target in solid tumors plays a key role in adaptation to ERS. Single-stranded RNAs usually modulate posttranscriptional of the gene activity. miR-30c-2-3p has been demonstrated to inhibit the expression of XBP1. Here, we evaluated the effect of miR-30c-2-3p on controlling XBP1-CHOP-BIM and its apoptotic effects on ovarian cancer cell lines during ERS. The ER stress was assessed using Thioflavin T staining in OVCAR3 and SKOV3 cells. The expression of ER stress genes was measured by QRT-PCR. The protein levels of XBP1(s), BIP/GRP78, CHOP, and BIM were evaluated using Western blotting. Cell viability and apoptosis in STF-083010 and Tunicamycin (Tm) co-treated cells were evaluated using BrdU, MTT, Annexin V-FITC/PI staining, and caspase-12 and -3 activities assays. We found that miR-30c-2-3p significantly decreased the folding capacity of ER, leading to ERS intensification (P<0.05). Additionally, the Western blot analysis showed the modest up-regulation of CHOP and BIM with pro-apoptotic activity and down-regulation of the BIP protein. Furthermore, mimic miR-30c-2-3p transfection not only decreased cell proliferation but also induced cell death in ovarian cancer cells in response to the Tm-treatment. Our results indicated that the apoptotic pathway was induced possibly through activation of caspases -12 and -3 and elevation of the Bax/Bcl-2 ratio. Overall, the present paper adds new evidence to the possible treatment of miR-30c-2-3p via impeding the XBP1 transcription in ovarian cancer cells provoking apoptotic pathways by XBP1/CHOP/BIM mediators.