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- W2072812114 abstract "GRP78, a major endoplasmic reticulum (ER) chaperone and signaling regulator, is commonly over-expressed in cancer and contributes to cancer cell proliferation, survival and tumorigenesis. Moreover, induction of GRP78 by a variety of anti-cancer drugs, including histone deacetylase inhibitors, confers chemo-resistance to cancer. Thus, targeting GRP78 to inhibit tumor survival and proliferation, sensitize tumor cells to chemotherapeutic drugs and consequently induce apoptosis serves as a promising avenue in anti-cancer therapy. As endogenous regulators, microRNAs (miRNAs) play important roles in modulating gene expression; therefore, we sought to identify miRNA(s) that target GRP78. We report that multiple miRNAs (miR-30d, miR-181a, miR-199-5p) commonly down-regulated in human cancer cell lines can repress GRP78 and lead to increased apoptosis in C42B prostate cancer cells. Luciferase reporter assays indicate that these miRNAs act as negative regulators of GRP78 by directly targeting the 3′ untranslated region of GRP78. Importantly, the combination of multiple miRNAs cooperated resulting in greater inhibition on GRP78 than individual miRNAs, suggesting the efficacy of tumor suppression by combined miRNAs. In addition, we showed that transfection of the multiple miRNAs in C42B cells increased sensitivity of cancer cells to trichostatin A (TSA), a histone deacetylase inhibitor, induced apoptosis, and inhibited cell proliferation and colony formation. Therefore, we suggest that delivery of combinations of specific miRNAs could be a novel anti-cancer approach capable of suppressing GRP78 and in turn inhibiting GRP78-mediated tumorigenesis.Citation Format: Sheng-Fang Su, Amy S. Lee, Gangning Liang. Defining specific microRNAs that cooperatively regulate GRP78, an ER chaperone and signaling regulator, in cancer [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A8." @default.
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- W2072812114 date "2012-01-08" @default.
- W2072812114 modified "2023-09-26" @default.
- W2072812114 title "Abstract A8: Defining specific microRNAs that cooperatively regulate GRP78, an ER chaperone and signaling regulator, in cancer" @default.
- W2072812114 doi "https://doi.org/10.1158/1538-7445.nonrna12-a8" @default.
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