PMID- 33931593 OWN - NLM STAT- MEDLINE DCOM- 20211005 LR - 20211005 IS - 2041-4889 (Electronic) VI - 12 IP - 5 DP - 2021 Apr 30 TI - MIR99AHG is a noncoding tumor suppressor gene in lung adenocarcinoma. PG - 424 LID - 10.1038/s41419-021-03715-7 [doi] LID - 424 AB - Little is known about noncoding tumor suppressor genes. An effective way to identify these genes is by analyzing somatic copy number variation (CNV)-related noncoding genes. By integrated bioinformatics analyses of differentially expressed long noncoding RNAs (lncRNAs) and arm-level CNVs in lung adenocarcinoma (LUAD), we identified a potential antitumor gene, MIR99AHG, encoding lncRNA MIR99AHG as well as a miR-99a/let-7c/miR-125b2 cluster on chromosome 21q. All four of these transcripts were downregulated in LUAD tissues partly due to the copy number deletion of the MIR99AHG gene. Both MIR99AHG and miR-99a expression was positively correlated with the survival of LUAD patients. MIR99AHG suppressed proliferation and metastasis and promoted autophagy both in vitro and in vivo. Mechanistically, the interaction between MIR99AHG and ANXA2 could accelerate the ANXA2-induced ATG16L(+) vesicle biogenesis, thus promoting phagophore assembly. Additionally, miR-99a targeted a well-known autophagy suppressor, mammalian target of rapamycin (mTOR), thereby synergistically promoting autophagy and postponing LUAD progression with MIR99AHG. In summary, MIR99AHG emerges as a noncoding tumor suppressor gene in LUAD, providing a new strategy for antitumor therapy. FAU - Han, Chencheng AU - Han C AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Li, Hong AU - Li H AD - Department of Thoracic Surgery, the Third Affiliated Hospital of Soochow University, Changzhou, China. AD - Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Ma, Zhifei AU - Ma Z AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Dong, Guozhang AU - Dong G AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Wang, Qianyun AU - Wang Q AD - Department of Thoracic Surgery, the Third Affiliated Hospital of Soochow University, Changzhou, China. FAU - Wang, Siwei AU - Wang S AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Fang, Panqi AU - Fang P AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Li, Xiang AU - Li X AD - Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Chen, Hao AU - Chen H AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Liu, Tongyan AU - Liu T AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. AD - Department of Science and technology, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Xu, Lin AU - Xu L AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Wang, Jie AU - Wang J AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. 51665070@qq.com. AD - Department of Science and technology, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. 51665070@qq.com. AD - Biobank of Lung Cancer, Jiangsu Biobank of Clinical Resources, Nanjing, China. 51665070@qq.com. FAU - Wang, Jun AU - Wang J AUID- ORCID: 0000-0002-5975-542X AD - Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. drwangjun@njmu.edu.cn. FAU - Yin, Rong AU - Yin R AUID- ORCID: 0000-0002-9744-4251 AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. rong_yin@njmu.edu.cn. AD - Department of Science and technology, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. rong_yin@njmu.edu.cn. AD - Biobank of Lung Cancer, Jiangsu Biobank of Clinical Resources, Nanjing, China. rong_yin@njmu.edu.cn. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. rong_yin@njmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210430 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (MicroRNAs) SB - IM MH - Adenocarcinoma of Lung/*genetics/pathology MH - Animals MH - Cell Movement/physiology MH - Cell Proliferation/physiology MH - *Genes, Tumor Suppressor MH - Humans MH - Lung Neoplasms/*genetics/pathology MH - Mice MH - Mice, Nude MH - MicroRNAs/*genetics PMC - PMC8087685 COIS- The authors declare no competing interests. EDAT- 2021/05/02 06:00 MHDA- 2021/10/06 06:00 PMCR- 2021/04/30 CRDT- 2021/05/01 05:59 PHST- 2020/11/12 00:00 [received] PHST- 2021/04/12 00:00 [accepted] PHST- 2021/04/09 00:00 [revised] PHST- 2021/05/01 05:59 [entrez] PHST- 2021/05/02 06:00 [pubmed] PHST- 2021/10/06 06:00 [medline] PHST- 2021/04/30 00:00 [pmc-release] AID - 10.1038/s41419-021-03715-7 [pii] AID - 3715 [pii] AID - 10.1038/s41419-021-03715-7 [doi] PST - epublish SO - Cell Death Dis. 2021 Apr 30;12(5):424. doi: 10.1038/s41419-021-03715-7.