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LncRNA CISAL Inhibits BRCA1 Transcription by Forming a Tertiary Structure at Its Promoter.

ABSTRACT: Cisplatin-based neoadjuvant chemotherapy has been shown to improve survival in patients with squamous cell carcinoma (SCC), but clinical biomarkers to predict chemosensitivity remain elusive. Here, we show the long noncoding RNA (lncRNA) LINC01011, which we termed cisplatin-sensitivity-associated lncRNA (CISAL), controls mitochondrial fission and cisplatin sensitivity by inhibiting BRCA1 transcription in tongue SCC (TSCC) models. Mechanistically, we found CISAL directly binds the BRCA1 promoter and forms an RNA-DNA triplex structure, sequestering BRCA1 transcription factor-GABPA away from the downstream regulatory binding region. Importantly, the clinical relevance of these findings is suggested by the significant association of CISAL and BRCA1 expression levels in TSCC tumors with neoadjuvant chemosensitivity and overall survival. We propose a new model where lncRNAs are tethered at gene promoter by RNA-DNA triplex formation, spatially sequestering transcription factors away from DNA-binding sites. Our study uncovers the potential of CISAL-BRCA1 signaling as a potential target to predict or improve chemosensitivity.

SUBMITTER: Fan S

PROVIDER: S-EPMC7033639 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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lncRNA CISAL Inhibits BRCA1 Transcription by Forming a Tertiary Structure at Its Promoter.

Fan Song S Tian Tian T Lv Xiaobin X Lei Xinyuan X Yang Zhaohui Z Liu Mo M Liang Faya F Li Shunrong S Lin Xiaofeng X Lin Zhaoyu Z Xie Shule S Li Bowen B Chen Weixiong W Pan Guokai G Lin Xinyu X Ou Zhanpeng Z Zhang Yin Y Peng Yu Y Xiao Liping L Zhang Lizao L Sun Sheng S Zhang Hanqing H Lin Sigeng S Li Qunxing Q Zeng Binghui B Kontos Filippos F Ruan Yi Y Ferrone Soldano S Lin Dechen D Tannous Bakhos A BA Li Jinsong J

iScience 20200111 2

Cisplatin-based neoadjuvant chemotherapy has been shown to improve survival in patients with squamous cell carcinoma (SCC), but clinical biomarkers to predict chemosensitivity remain elusive. Here, we show the long noncoding RNA (lncRNA) LINC01011, which we termed cisplatin-sensitivity-associated lncRNA (CISAL), controls mitochondrial fission and cisplatin sensitivity by inhibiting BRCA1 transcription in tongue SCC (TSCC) models. Mechanistically, we found CISAL directly binds the BRCA1 promoter ...[more]

PMID: 32000125

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Dataset Information

LncRNA CISAL Inhibits BRCA1 Transcription by Forming a Tertiary Structure at Its Promoter.

Publications

lncRNA CISAL Inhibits BRCA1 Transcription by Forming a Tertiary Structure at Its Promoter.

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