bims-istrec Biomed News
on Integrated stress response in cancer
Issue of 2021–11–21
two papers selected by
the Vincenzo Ciminale lab, Istituto Oncologico Veneto
  1. Endoplasmic reticulum stress promotes sorafenib resistance via miR-188-5p/hnRNPA2B1-mediated upregulation of PKM2 in hepatocellular carcinoma.
  2. Knockdown of Oligosaccharyltransferase Subunit Ribophorin 1 Induces Endoplasmic-Reticulum-Stress-Dependent Cell Apoptosis in Breast Cancer.
  1. Mol Ther Nucleic Acids. 2021 Dec 03. 26 1051-1065
    Endoplasmic reticulum stress promotes sorafenib resistance via miR-188-5p/hnRNPA2B1-mediated upregulation of PKM2 in hepatocellular carcinoma.
    Bei Zhou, Donghui Lu, Anqi Wang, Jie Cui, Li Zhang, Jian Li, Lulu Fan, Wei Wei, Jiatao Liu, Guoping Sun.
      Emerging evidence has shown that endoplasmic reticulum (ER) stress promotes sorafenib resistance in hepatocellular carcinoma (HCC). However, the underlying mechanisms are poorly understood. The purpose of this study was to explore the mechanism by which ER stress promotes sorafenib resistance in HCC. We found that pyruvate kinase isoform M2 (PKM2) was highly expressed in human HCC tissues and co-related with worse clinicopathologic features and overall survival. Activation of ER stress positively correlated with PKM2 expression both in HCC tissue samples and tunicamycin (TM)-induced HCC cell lines. PKM2 knockdown increased sorafenib-induced apoptosis and decreased the ability of colony formation, while upregulation of PKM2 reverses this phenomenon. Furthermore, high-throughput sequencing identified that activation of ER stress significantly downregulated the expression of miR-188-5p in HCC cells. According to bioinformatics analysis and dual-luciferase assays, we further confirmed that hnRNPA2B1 is the target gene of miR-188-5p. Downregulating the expression of hnRNPA2B1 with siRNA could decrease the expression of PKM2 and enhance sorafenib-induced apoptosis in HepG2 cells. Our study demonstrated that ER stress could promote sorafenib resistance through upregulating PKM2 via miR-188-5p/hnRNPA2B1. Therefore, targeting the miR-188-5p/hnRNPA2B1/PKM2 pathway and ER stress may prove instrumental in overcoming sorafenib resistance in HCC treatment.
    Keywords:  PKM2; endoplasmic reticulum stress; hepatocellular carcinoma; hnRNPA2B1; miR-188-5p; sorafenib
    DOI:  https://doi.org/10.1016/j.omtn.2021.09.014
  2. Front Oncol. 2021 ;11 722624
    Knockdown of Oligosaccharyltransferase Subunit Ribophorin 1 Induces Endoplasmic-Reticulum-Stress-Dependent Cell Apoptosis in Breast Cancer.
    Jiajun Ding, Jiahui Xu, Qiaodan Deng, Wei Ma, Rui Zhang, Xueyan He, Suling Liu, Lixing Zhang.
      Ribophorin 1 (RPN1) is a major part of Oligosaccharyltransferase (OST) complex, which is vital for the N-linked glycosylation. Though it has been verified that the abnormal glycosylation is closely related to the development of breast cancer, the detail role of RPN1 in breast cancer remains unknown. In this study, we explored the public databases to investigate the relationship between the expression levels of OST subunits and the prognosis of breast cancer. Then, we focused on the function of RPN1 in breast cancer and its potential mechanisms. Our study showed that the expression of several OST subunits including RPN1, RPN2, STT3A STT3B, and DDOST were upregulated in breast cancer samples. The protein expression level of RPN1 was also upregulated in breast cancer. Higher expression of RPN1 was correlated with worse clinical features and poorer prognosis. Furthermore, knockdown of RPN1 suppressed the proliferation and invasion of breast cancer cells in vitro and induced cell apoptosis triggered by endoplasmic reticulum stress. Our results identified the oncogenic function of RPN1 in breast cancer, implying that RPN1 might be a potential biomarker and therapeutic target for breast cancer.
    Keywords:  apoptosis; breast cancer; endoplasmic reticulum stress; oligosaccharyltransferase complex; ribophorin 1
    DOI:  https://doi.org/10.3389/fonc.2021.722624
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