PMID- 31959918 OWN - NLM STAT- MEDLINE DCOM- 20210114 LR - 20210119 IS - 2041-4889 (Electronic) VI - 11 IP - 1 DP - 2020 Jan 20 TI - Long noncoding RNA FOXD2-AS1 enhances chemotherapeutic resistance of laryngeal squamous cell carcinoma via STAT3 activation. PG - 41 LID - 10.1038/s41419-020-2232-7 [doi] LID - 41 AB - Laryngeal squamous cell carcinoma (LSCC) is a common head and neck cancer. Despite recently improved management of LSCC, chemotherapy resistance of patients remains a challenge. In this study, we identified that long noncoding RNA FOXD2-AS1 regulates LSCC therapeutic resistance by augmenting LSCC stemness. LSCC chemotherapy-resistant patients showed increased FOXD2-AS1 expression compared with that in chemotherapy-sensitive patients, which predicted poor prognosis. Gain- or loss-of-function experiments showed that upregulated FOXD2-AS1 maintained cancer stemness, reducing the response to chemotherapy, while FOXD2-AS1 downregulation had the opposite effects. FOXD2-AS1 acted as a scaffold for STAT3 and PRMT5, promoting STAT3 transcriptional activity, which is essential to maintain cancer stemness and promote chemotherapeutic resistance. Interfering with FOXD2-AS1 using short hairpin RNA rescued LSCC's chemotherapeutic sensitivity. Thus, FOXD2-AS1 promotes LSCC chemotherapeutic resistance and is an upstream activator of STAT3, making FOXD2-AS1 a potential therapeutic target to improve the chemotherapy effect in LSCC patients. FAU - Li, Rui AU - Li R AD - Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China. AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. FAU - Chen, Shuwei AU - Chen S AD - Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. AD - State Key Laboratory of Oncology in South China, Guangzhou, China. AD - Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. FAU - Zhan, Jiandong AU - Zhan J AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. FAU - Li, Xinghua AU - Li X AD - Department of Radiotherapy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China. FAU - Liu, Wenlin AU - Liu W AD - Department of Otorhinolaryngology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou, China. FAU - Sheng, Xiaoli AU - Sheng X AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. FAU - Lu, Zhongming AU - Lu Z AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. FAU - Zhong, Rong AU - Zhong R AD - Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China. AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. FAU - Chen, Liangsi AU - Chen L AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. FAU - Luo, Xiaoning AU - Luo X AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. FAU - Hu, Yameng AU - Hu Y AD - Department of Biochemistry, Zhongshan school of medicine, Sun Yat-sen University, Guangzhou, China. FAU - Ouyang, Ying AU - Ouyang Y AD - Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China. FAU - Liu, Tao AU - Liu T AD - Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China. taoliu18@126.com. AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. taoliu18@126.com. FAU - Zhang, Quan AU - Zhang Q AD - Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. zhangquan@sysucc.org.cn. AD - State Key Laboratory of Oncology in South China, Guangzhou, China. zhangquan@sysucc.org.cn. AD - Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. zhangquan@sysucc.org.cn. FAU - Zhang, Siyi AU - Zhang S AUID- ORCID: 0000-0001-8669-5285 AD - Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China. zhangsiyi@gdph.org.cn. AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. zhangsiyi@gdph.org.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200120 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (RNA, Long Noncoding) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) RN - 0 (long non-coding RNA FOXD2-AS1, human) RN - EC 2.1.1.319 (PRMT5 protein, human) RN - EC 2.1.1.319 (Protein-Arginine N-Methyltransferases) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Animals MH - Carcinoma, Squamous Cell/*genetics/*pathology MH - Cell Line, Tumor MH - Cisplatin/pharmacology/therapeutic use MH - Drug Resistance, Neoplasm/*genetics MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Laryngeal Neoplasms/*drug therapy/*genetics MH - Male MH - Mice, Inbred BALB C MH - Mice, Nude MH - Models, Biological MH - Neoplastic Stem Cells/drug effects/metabolism/pathology MH - Prognosis MH - Protein Binding/drug effects MH - Protein-Arginine N-Methyltransferases/metabolism MH - RNA, Long Noncoding/genetics/*metabolism MH - STAT3 Transcription Factor/*metabolism MH - Transcription, Genetic/drug effects MH - Up-Regulation/genetics PMC - PMC6971019 COIS- The authors declare that they have no conflict of interest. EDAT- 2020/01/22 06:00 MHDA- 2021/01/15 06:00 PMCR- 2020/01/20 CRDT- 2020/01/22 06:00 PHST- 2019/09/02 00:00 [received] PHST- 2019/12/20 00:00 [accepted] PHST- 2019/12/18 00:00 [revised] PHST- 2020/01/22 06:00 [entrez] PHST- 2020/01/22 06:00 [pubmed] PHST- 2021/01/15 06:00 [medline] PHST- 2020/01/20 00:00 [pmc-release] AID - 10.1038/s41419-020-2232-7 [pii] AID - 2232 [pii] AID - 10.1038/s41419-020-2232-7 [doi] PST - epublish SO - Cell Death Dis. 2020 Jan 20;11(1):41. doi: 10.1038/s41419-020-2232-7.