Biology subjects

Huang, M.-S.

Publications and source records attributed to Huang, M.-S..

3 recordsLinked to original sources

bioRxiv2019

TAO Kinase 3 Overexpression Is a Poor Prognosis Marker for Lung Adenocarcinoma and Predicts Paclitaxel Resistance

High expression of TAOK3 has been observed in several cancers, but very little about TAOK3-involved mechanisms has been reported. In this study, we investigated the role of TAOK3 in the therapeutic effect of paclitaxel treatment. Protein expression of TAOK3 was evaluated among 121 patients by using immunohistochemical staining. TAOK3 expression was estimated by analyzing the genes expression and its correlation with the IC50 of paclitaxel in cells. The expression of TAOK3 in lung cancer was highly correlated with poor overall survival, progression-free survival, and recurrence rate in lung cancer patients. The expression level of TAOK3 was positively correlated with paclitaxel resistance in the lung cancer cell lines. The depletion of TAOK3 could enhance the sensitivity of paclitaxel in lung cancer and vice versa. TAOK3 expression is associated with paclitaxel-resistance and could be a clinical predictor for disease recurrence and a potential therapeutic target in lung cancer.

cancer biology↗

bioRxiv2018

A nonsense mutant of the hepatitis B virus large S protein antagonizes multiple tumor suppressor pathways through c-Jun activation domain-binding protein1

Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). Previous studies have identified recurrent nonsense mutations in the HBV large S (LHBs) gene from the liver from HBV core antigen-positive HCC patients. These nonsense mutants have been shown to be oncogenic in mouse xenograft models using a mouse embryonic fibroblast cell line. Here, we expressed in a liver cell line Huh-7 a carboxy terminally truncated protein from a nonsense mutant of the LHBs gene, sW182* (stop codon at tryptophane-182). Although the sW182* protein appeared not to be very stable in the cultured liver cells, we confirmed that the protein can be highly expressed and retained for a prolonged period of time in the hepatocytes in the mouse liver, indicating its stable nature in the physiological condition.\n\nIn the Huh-7 cells, the sW182* mutant downregulated tumor suppressors p53 and Smad4. This downregulation was reversed by a proteasome inhibitor MG132, implying the involvement of proteasome-based protein degradation in the observed regulation of the tumor suppressors. On the other hand, we found that c-Jun activation domain-binding protein 1 (Jab1) physically interacts with the sW182*, but not wild-type LHBs. RNA interference (RNAi) of Jab1 restored the levels of the downregulated p53 and Smad4. The sW182* mutant inhibited the promoter activity of downstream target genes of the tumor suppressors. Consistently, Jab1 RNAi reversed the inhibition.\n\nThese results suggest that the LHBs nonsense mutant antagonizes the tumor suppressor pathways through Jab1 in the liver contributing to HCC development.

molecular biology↗

bioRxiv2017

Adenylate kinase-4 modulates oxidative stress and stabilizes HIF-1α to drive lung cancer metastasis

Disrupting signaling axes that are essential for tumor metastasis may provide therapeutic opportunity to cure cancer. We previously identified adenylate kinase 4 (AK4) as a biomarker of metastasis in lung cancer. Here we analyze AK4-associated metabolic gene signature and reveal HIF-1 is transcriptionally activated and associated with poor prognosis in lung adenocarcinoma patients. Overexpression of AK4 shifts metabolism towards aerobic glycolysis and elevates intracellular reactive oxygen species (ROS), which stabilizes and exaggerates HIF1- protein expression and concurrently drives epithelial-to-mesenchymal transition (EMT) in hypoxia. Furthermore, overexpression of AK4 reduces hypoxic necrosis in tumors and promotes liver metastasis in vivo. Connectivity map analysis of AK4 gene signature identifies Withaferin-A as a potential compound to inhibit AK4-HIF-1 signaling axis, which then shows promising anti-metastatic potency in an orthotopic xenograft model of lung cancer. Our findings offer an alternative strategy to impair lung cancer metastasis via targeting AK4-HIF-1 axis.

cancer biology↗