Transcription factor ZNF703 activates linc-UBC1 to stimulate the progression of glioma.

OBJECTIVE: To investigate the role of the transcription factor Zinc finger 703 (ZNF703) in influencing the progression of glioma by regulating linc-UBC1 level. MATERIALS AND METHODS: Linc-UBC1 level in glioma with different staging and tumor sizes was determined. The potential influences of linc-UBC1 on viability, cell cycle progression, and invasiveness of glioma cells were evaluated. Through RNA binding protein immunoprecipitation (RIP) assay and Dual-Luciferase reporter gene assay, the interaction between ZNF703 and linc-UBC1 was assessed. The rescue experiments were conducted to identify the role of ZNF703 in regulating cellular performances of glioma by interacting with linc-UBC1. RESULTS: Linc-UBC1 was highly expressed in glioma. Its level was higher in glioma with larger tumor size or advanced staging. The knockdown of linc-UBC1 reduced viability, arrested cell cycle in the G0/G1 phase, and attenuated invasiveness of U87 and LN229 cells. The presence of the binding sites was observed in the promoter regions of ZNF703 and linc-UBC1. The overexpression of ZNF703 could alleviate the inhibited proliferative and invasive potentials in U87 and LN229 cells with the linc-UBC1 knockdown. CONCLUSIONS: The transcription factor ZNF703 promotes the proliferative and invasive potentials in glioma cells by regulating the transcriptional activity of linc-UBC1.

MiR-372-3p promotes tumor progression by targeting LATS2 in colorectal cancer.

OBJECTIVE: Many studies suggest that microRNAs can promote the malignant development of tumors. MiRNA-372-3p (miR-372-3p) has been proved to be associated with a variety of cancers. However, the role of miR-372-3p in colorectal cancer (CRC) is unclear. PATIENTS AND METHODS: We analyzed the expression of miR-372-3p in CRC tissues and several CRC cell lines by quantitative Real Time-PCR. The relationship between miR-372-3p and clinical pathology was also analyzed in CRC patients. Kaplan-Meier analysis and Cox multivariate analysis were used to evaluate the prognostic significance of miR-372-3p in CRC. Next, we investigated the biological function of miR-372-3p, including cell proliferation, migration, and invasion and analyzed its potential molecular mechanism in vivo and in vitro. RESULTS: Our data showed that the expression of miR-372-3p was dramatically increased in CRC tissues compared with normal tissues. Moreover, the high expression of miR-372-3p was significantly correlated with tumor size and differentiation. Kaplan-Meier analysis showed that the high miR-372-3p expression group patients had a significantly shorter recurrence-free survival (RFS) and disease-specific survival (DSS) than those with the low miR-372-3p group. The analysis of the prognostic factors revealed that miR-372-3p was an independent prognostic factor for RFS and DSS in CRC patients. The knockdown of miR-372-3p inhibited the proliferation, migration, and invasion in HCT116 and SW480 cells. Interestingly, the overexpression of LATS2 partially reversed the miR-372-3p -mediated cell proliferation, migration, and invasion of CRC. Besides, the Hippo signaling pathway was demonstrated to be activated by decreasing of miR-372-3p in CRC. Thus, our study revealed that miR-372-3p is involved in CRC progression by inhibiting the Hippo signaling pathway through its target LATS2. MiR-372-3p and its target genes with signaling pathways are new hope for precise treatment of CRC. CONCLUSIONS: The upregulation of miR-372-3p was involved in the process of CRC progression by inhibiting the Hippo signaling pathway through inhibition of LATS2. We showed that miR-372-3p and its target genes with signaling pathways are a novel hope for precise treatment of CRC.

HGF alleviates renal interstitial fibrosis via inhibiting the TGF-ß1/SMAD pathway.

OBJECTIVE: To study the role of HGF (stem cell growth factor) in renal interstitial fibrosis and to explore its underlying mechanism. MATERIALS AND METHODS: A unilateral ureteral obstruction (UUO) mouse model was first constructed, and kidney samples of mice were then collected. Fibrosis-related indicators in UUO mice kidney were detected by Western blot. The mRNA and protein levels of HGF in UUO mice were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR) and Western blot, respectively. The HGF overexpression mouse model was established by using UUO mice. For in vitro experiments, fibrosis-related indicators and the expression of HGF were detected in transforming growth factor-ß1 (TGF-ß1)-induced NRK-52E cells. Finally, a p-SMAD3 knockdown mouse model was established to confirm whether p-SMAD3 was involved in HGF-regulated renal interstitial fibrosis. RESULTS: The expression levels of HGF and α-SMA (α-smooth muscle actin) were both significantly increased in UUO mice, while E-cadherin expression was significantly decreased, which were consistent with results of in vitro experiments. Overexpression of HGF remarkably decreased the protein and mRNA levels of α-SMA in fibrotic NRK-52E cells. After overexpression of HGF in UUO mice, α-SMA was remarkably downregulated, whereas E-cadherin was significantly upregulated. Further, results also demonstrated that HGF was upregulated and α-SMA was downregulated after p-SMAD3 knockdown in UUO mice. CONCLUSIONS: HGF is highly expressed during renal interstitial fibrosis, which may suppress renal interstitial fibrosis by inhibiting the TGF-ß1/SMAD signaling pathway.