PMID- 28716024 OWN - NLM STAT- MEDLINE DCOM- 20180413 LR - 20220408 IS - 1476-4598 (Electronic) IS - 1476-4598 (Linking) VI - 16 IP - 1 DP - 2017 Jul 17 TI - MiR-661 promotes tumor invasion and metastasis by directly inhibiting RB1 in non small cell lung cancer. PG - 122 LID - 10.1186/s12943-017-0698-4 [doi] LID - 122 AB - BACKGROUND: Aberrant microRNA expression has been implicated in metastasis of cancers. MiR-661 accelerates proliferation and invasion of breast cancer and ovarian cancer, while impedes that of glioma. Its role in non small cell lung cancer (NSCLC) and underlying mechanism are worthy elucidation. METHODS: Expression of miR-661 was measured with real-time PCR in both NSCLC tissues and cell lines. The effects of miR-661 on migration, invasion and metastasis capacity of NSCLC were evaluated using wound healing, transwell assay and animal models. Dual reporter luciferase assay and complementary experiments were performed to validate RB1 as a direct target of miR-661 for participation in the progression of NSCLC. RESULTS: MiR-661 was upregulated in NSCLC tissues as compared to paired adjacent tissues and associated with shorter overall survival. Furthermore, miR-661 promoted proliferation, migration and metastasis of NSCLC. Then, we identified RB1 as a direct target of miR-661 through which miR-661 affected EMT process and metastasis of NSCLC. RB1 interacted with E2F1 and both could mediate EMT process in NSCLC. CONCLUSION: MiR-661 promotes metastasis of NSCLC through RB/E2F1 signaling and EMT events, thus may serves as a negative prognostic factor and possible target for treatment of NSCLC patient. FAU - Liu, Feiye AU - Liu F AD - Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern medical University, Guangdong, 510315, China. FAU - Cai, Yanjun AU - Cai Y AD - Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern medical University, Guangdong, 510315, China. AD - Center for Geriatrics, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangdong, 510010, China. FAU - Rong, Xiaoxiang AU - Rong X AD - Department of Oncology, Nanfang Hospital, Southern medical University, Guangdong, 510515, China. FAU - Chen, Jinzhang AU - Chen J AD - Department of Oncology, Nanfang Hospital, Southern medical University, Guangdong, 510515, China. FAU - Zheng, Dayong AU - Zheng D AD - Department of Oncology, Nanfang Hospital, Southern medical University, Guangdong, 510515, China. FAU - Chen, Lu AU - Chen L AD - Center for Geriatrics, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangdong, 510010, China. FAU - Zhang, Junyi AU - Zhang J AD - Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern medical University, Guangdong, 510315, China. FAU - Luo, Rongcheng AU - Luo R AD - Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern medical University, Guangdong, 510315, China. FAU - Zhao, Peng AU - Zhao P AD - Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, 310003, China. FAU - Ruan, Jian AU - Ruan J AD - Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern medical University, Guangdong, 510315, China. software23@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170717 PL - England TA - Mol Cancer JT - Molecular cancer JID - 101147698 RN - 0 (E2F1 Transcription Factor) RN - 0 (E2F1 protein, human) RN - 0 (MIRN661 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RB1 protein, human) RN - 0 (Retinoblastoma Binding Proteins) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Aged MH - Animals MH - Base Sequence MH - Carcinoma, Non-Small-Cell Lung/*genetics/*pathology MH - Cell Line, Tumor MH - E2F1 Transcription Factor/metabolism MH - Epithelial-Mesenchymal Transition/genetics MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Lung Neoplasms/*genetics/*pathology MH - Male MH - Mice, Inbred BALB C MH - Mice, Nude MH - MicroRNAs/genetics/*metabolism MH - Middle Aged MH - Neoplasm Invasiveness MH - Neoplasm Metastasis MH - Prognosis MH - Protein Binding MH - Retinoblastoma Binding Proteins/*metabolism MH - Ubiquitin-Protein Ligases/*metabolism MH - Up-Regulation/genetics PMC - PMC5514511 OTO - NOTNLM OT - E2F1 OT - Metastasis OT - Non small cell lung cancer OT - RB OT - miR-661 COIS- AUTHORS' INFORMATION: Not applicable. ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The study was approved by Research Ethics Committee of Nanfang Hospital and SMUCC. All samples were used according to the ethical guidelines of the 1975 Declaration of Helsinki and obtained with the patients' understanding that it might be published. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/07/19 06:00 MHDA- 2018/04/14 06:00 PMCR- 2017/07/17 CRDT- 2017/07/19 06:00 PHST- 2016/12/20 00:00 [received] PHST- 2017/07/11 00:00 [accepted] PHST- 2017/07/19 06:00 [entrez] PHST- 2017/07/19 06:00 [pubmed] PHST- 2018/04/14 06:00 [medline] PHST- 2017/07/17 00:00 [pmc-release] AID - 10.1186/s12943-017-0698-4 [pii] AID - 698 [pii] AID - 10.1186/s12943-017-0698-4 [doi] PST - epublish SO - Mol Cancer. 2017 Jul 17;16(1):122. doi: 10.1186/s12943-017-0698-4.