Search

Tumor recurrence and metastasis after surgical resection are the major causes for the cancer-related death of hepatocellular carcinoma (HCC). Thus, better understanding the mechanisms involved in tumor progression will benefit to improve HCC treatment. Accumulating evidence demonstrates that microRNAs (miRNAs) play critical roles in the development and progression of HCC. However, the function of miR-519c-3p in HCC and its related mechanism remain unexplored. Here, we reported that miR-519c-3p was strongly overexpressed in HCC tissues, which was significantly correlated with poor prognosis and clinicopathological features including tumor size ≥5 cm, vascular invasion and advanced tumor-node-metastasis (TNM) stages (III + IV). Furthermore, the elevated levels of miR-519c-3p were observed in HCC cell lines. Subsequently, gain- or loss-of-function assays demonstrated that miR-519c-3p promoted HCC cell proliferation, migration as well as invasion in vitro, and facilitated the growth and metastasis of HCC cells in vivo. Mechanistically, B-cell translocation gene 3 (BTG3) was identified as a direct downstream target of miR-519c-3p. The level of BTG3 mRNA was downregulated in HCC and negatively correlated with miR-519c-3p expression. Western blotting confirmed that BTG3 was negatively regulated by miR-519c-3p in HCC cells. Luciferase reporter assays illustrated the direct interaction between miR-519c-3p and the 3'UTR of BTG3 mRNA. Recuse experiments demonstrated that BTG3 mediated the promoting effects of miR-519c-3p on the proliferation and motility of HCC cells. Collectively, our results suggest that miR-519c-3p functions as a tumor promotor in regulating the growth and metastasis of HCC by targeting BTG3, and potentially serves as a novel therapeutic target for HCC., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

5-Fluorouracil (5-FU)-based chemotherapy has always been the first-line treatment of colorectal cancer (CRC). However, the occurrence of clinical 5-FU resistance is a major reason for CRC therapy failure. This study intended to explore the possible role of long non-coding RNA HOTAIRM1 (HOTAIRM1) in the pathogenesis of 5-FU resistant CRC and its underlying mechanism. Our data showed that HOTAIRM1 was downregulated in CRC tissues and cell lines (HCT116 and SW480), and even lower in 5-FU resistant CRC tissues and cell lines (HCT116/5-FU and SW480/5-FU). In vitro, effects of HOTAIRM1 dysregulation in 5-FU resistant CRC cells were investigated and its overexpression could reduce cell viability, invasion, migration, and multi-drug resistance as evidenced by MTT assay, Transwell assay, epithelial-mesenchymal transition (EMT), and western blot analyzing expression of drug-resistant genes MRP1 and MDR1, respectively. Mechanically, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) identified that HOTAIRM1 and B-cell translocation gene 3 (BTG3) were target genes of miR-17-5p. Moreover, miR-17-5p was upregulated and BTG3 was downregulated in HCT116/5-FU and SW480/5-FU cells. Silencing of miR-17-5p showed suppressive role on cell viability, invasion, migration, and multi-drug resistance in HCT116/5-FU and SW480/5-FU cells, which could be abolished by HOTAIRM1 knockdown. Similarly, ectopic expression of miR-17-5p reversed BTG3-mediated inhibition on cell viability, invasion, migration, and multi-drug resistance. In vivo, the tumorigenesis of HCT116/5-FU cells when highly expressed HOTAIRM1 by lentivirus infection was inhibited through downregulating miR-17-5p and upregulating BTG3. In conclusion, HOTAIRM1 might act as a tumor-suppressor in 5-FU resistant CRC cells in vitro and in vivo through downregulating miR-17-5p/BTG3 pathway and inhibiting multi-drug resistance., (Copyright © 2019. Published by Elsevier Masson SAS.)

Neonatal brain hypoxia is a disease that affects the nervous system in children. Salidroside is a compound that has an anti-hypoxic effect, but the mechanism of salidroside in neonatal cerebral hypoxia is unclear. Hence, we investigated the regulatory effect and mechanism of salidroside on hypoxic-induced injury of neural stem cells (NSCs). NSCs derived from embryo 14 Sprague-Dawley rats were treated by hypoxia, followed by the treatment of 0.8 mM salidroside. The expression levels of miR-210 and BTG3 in NSCs were altered by transfection. Cell viability and apoptosis were examined by CCK-8 and flow cytometry analysis. qRT-PCR and Western blot were performed to assess the expression changes of miR-210, BTG3, apoptosis-related factors and core factors in PI3K/AKT/mTOR pathway. We found that hypoxia induced an apoptosis-dependent death in NSCs. Salidroside exerted bFGF-like effect, as it alleviated hypoxia-induced viability impairment and apoptosis in NSCs. Further studies showed that hypoxia plus salidroside elevated miR-210 expression, and the protective actions of salidroside on hypoxia-modulated death in NSCs were attenuated by miR-210 suppression, while were enhanced by miR-210 overexpression. Besides, BTG3 was negatively regulated by miR-210. Overexpression of BTG3 inhibited the activation of PI3K/AKT/mTOR signaling pathway; of contrast, suppression of BTG3 promoted it. To conclude, this study provide in vitro evidence that salidroside protected NSCs against hypoxia-induced injury by up-regulation of miR-210, which in turn inhibited the expression of BTG3 and activated PI3K/AKT/mTOR signaling pathway., (Copyright © 2018. Published by Elsevier Masson SAS.)