Search

Objective: Glycochenodeoxycholate acid (GCDA) is a toxic component in bile salts. It plays an important role in the development and progression of liver cancer. In this study, we investigated the underlying mechanism of GCDA in hepatocarcinogenesis and chemotherapy resistance. Materials and Methods: Cell proliferation was measured by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and clonality by Ki‐67 and colony‐formation assay. Apoptosis was examined by flow cytometry. Real‐time polymerase chain reaction (PCR) and western blot analysis were used to measure messenger RNA and protein levels, respectively. Short hairpin RNA was used to silence signal transducer and activator of transcription 3 (Stat3) expression. Results: Bile salts (GCDA) promoted the proliferation of hepatocellular carcinoma (HCC) cells (HepG2 and QGY‐7703), and GCDA treatment reduced the chemosensitivity of 5‐fluorouracil (5FU) in HepG2 and QGY‐7703 cells. GCDA upregulated the expression of antiapoptosis proteins Mcl‐1/Survivin/Bcl‐2. GCDA had no discernible effect on basal protein level or subcellular localization of phosphorylated Stat3. 5FU increased the apoptosis of HepG2 cells with silenced Stat3 expression, but GCDA‐induced chemoresistance was not reversed. Conclusions: GCDA‐reduced HCC cell chemosensitivity may occur by upregulating antiapoptosis proteins Mcl‐1/Survivin/Bcl‐2. Stat3 may be a target for enhancing the chemosensitivity of hepatocellular carcinoma cells, but GCDA‐induced chemoresistance is independent of Stat3. Our findings provide strong evidence that GCDA is an agonist for the survival of hepatocellular carcinoma (HCC) cells by promoting cell proliferation and activating antiapoptotic genes (Mcl‐1/Survivin/Bcl‐2) to protect neoplasm cells against apoptosis. Stat3 is involved in chemoresistance of HCC but is independent of GCDA‐induced chemoresistance. [ABSTRACT FROM AUTHOR]

Although long noncoding RNA (LncRNA) are important players in the initiation and progression of many pathological processes, the role of LncRNAENST00000453774.1 (LncRNA 74.1) in renal fibrosis still remains unclear. Lentivirus mediated LncRNA 74.1 overexpressing HK2 cells and overexpression mice models were constructed. HK2 cells induced by transforming growth factor‐β (TGF‐β) in vitro, and the mice UUO model in vivo were used to simulate renal fibrosis. The expression of LncRNA 74.1 was significantly downregulated in the TGF‐β‐induced HK‐2 cell fibrosis and clinical renal fibrosis specimens. LncRNA 74.1 overexpression obviously attenuated renal fibrosis in vitro and unilateral ureteral obstruction‐induced renal fibrosis in vivo. LncRNA 74.1 promoted reactive oxygen species defense by activating prosurvival autophagy then decreased ECM‐related proteins fibronectin and collagen I involved in renal fibrosis. We also found that Nrf2‐keap1 signaling played important roles in the remission of ECM mediated by LncRNA 74.1. This study indicates that LncRNA 74.1 downregulation would contribute to renal fibrosis and its overexpression might represent a novel anti‐fibrotic treatment in renal diseases. LncRNA 74.1 downregulation would contribute to renal fibrosis. Overexpression of LncRNA 74.1 might promote ROS defense via Nrf2‐keap1/HO‐1/NQO‐1 signaling by activating prosurvival autophagy then decrease the ECM related proteins, fibronectin and collagen I, involved in renal fibrosis. [ABSTRACT FROM AUTHOR]