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Start Over Author "Piwen Wang" Journal cell death and disease
2 results on '"Piwen Wang"'

1. Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA

Author

Qiongyu Hao, Piwen Wang, Pranabananda Dutta, Seyung Chung, Qun Li, Kun Wang, Jieqing Li, Wei Cao, Wenhong Deng, Qing Geng, Katrina Schrode, Magda Shaheen, Ke Wu, Donghui Zhu, Qiao-Hong Chen, Guanglin Chen, Yahya Elshimali, Jay Vadgama, and Yong Wu

Subjects
Cytology, QH573-671
Abstract

Abstract The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.

Published
2020
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2. Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA

Author

Kun Wang, Katrina M. Schrode, Qiongyu Hao, Piwen Wang, Jieqing Li, Yong Wu, Seyung Chung, Qun Li, Wenhong Deng, Jay Vadgama, Qiao-Hong Chen, Wei Cao, Ke Wu, Pranabananda Dutta, Magda Shaheen, Donghui Zhu, Qing Geng, Guanglin Chen, and Yahya Elshimali

Subjects
Cancer Research, Transcription, Genetic, AKT1, Diseases, Triple Negative Breast Neoplasms, Cytotoxicity, Triple-negative breast cancer, Cancer, Tumor, Chemistry, Drug discovery, lcsh:Cytology, TOR Serine-Threonine Kinases, Long non-coding RNA, Gene Expression Regulation, Neoplastic, Disease Progression, Neoplastic Stem Cells, Long Noncoding, RNA, Long Noncoding, Transcription, Biotechnology, Signal Transduction, Curcumin, Oncology and Carcinogenesis, Immunology, Antineoplastic Agents, Article, Cell Line, Cellular and Molecular Neuroscience, Breast cancer, Genetic, Cell Line, Tumor, Breast Cancer, microRNA, Genetics, medicine, Humans, lcsh:QH573-671, Protein kinase B, PI3K/AKT/mTOR pathway, Cell Proliferation, Sirolimus, Neoplastic, Base Sequence, Cell Biology, medicine.disease, MicroRNAs, Gene Expression Regulation, Cancer research, RNA, Biochemistry and Cell Biology, Proto-Oncogene Proteins c-akt
Abstract

The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.

Published
2020

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