PMID- 34012797 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220423 IS - 2218-6751 (Print) IS - 2226-4477 (Electronic) IS - 2218-6751 (Linking) VI - 10 IP - 4 DP - 2021 Apr TI - Let-7b-3p inhibits tumor growth and metastasis by targeting the BRF2-mediated MAPK/ERK pathway in human lung adenocarcinoma. PG - 1841-1856 LID - 10.21037/tlcr-21-299 [doi] AB - BACKGROUND: Lung cancer is a malignant tumor with the highest morbidity and mortality rates worldwide, of which lung adenocarcinoma (LUAD) is the most common subtype. Overall, current treatments of LUAD are not satisfactory; therefore, novel targets need to be explored. Let-7b-3p is an important member of the let-7 family of microRNAs (miRNAs), and has not been studied separately in LUAD. This study aimed to investigate the role and molecular mechanism of let-7b-3p in LUAD. METHODS: Herein, let-7b-3p expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) assays. MTT, colony formation assay, flow cytometry analysis, wound-healing, Transwell and in vivo experiments were conducted to assess let-7b-3p's function in LUAD. The downstream target TFIIB-related factor 2 (BRF2) was predicted using bioinformatics analyses and confirmed by dual-luciferase reporter assay and rescue experiments. Additionally, BRF2 was found to affect the MAPK/ERK pathway through transcriptome sequencing analysis and western blot (WB) assay. RESULTS: Let-7b-3p is downregulated in LUAD cells and tissue samples and low let-7b-3p expression is correlated with a poor prognosis in LUAD patients. Let-7b-3p suppresses the proliferation and metastasis of LUAD cells both in vivo and in vitro by directly targeting the BRF2-mediated MAPK/ERK pathway. CONCLUSIONS: Let-7b-3p inhibits the development of LUAD and is an ideal novel therapeutic target for the treatment of LUAD. CI - 2021 Translational Lung Cancer Research. All rights reserved. FAU - Li, Yongmeng AU - Li Y AD - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. FAU - Dong, Rui AU - Dong R AD - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. FAU - Lu, Ming AU - Lu M AD - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. FAU - Cheng, Chuanle AU - Cheng C AD - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. FAU - Feng, Zitong AU - Feng Z AD - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. FAU - Zhao, Renchang AU - Zhao R AD - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. FAU - Liang, Jinghui AU - Liang J AD - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. FAU - Han, Jingyi AU - Han J AD - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. FAU - Jiang, Jin AU - Jiang J AD - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. FAU - Xu-Welliver, Meng AU - Xu-Welliver M AD - Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA. FAU - Renaud, Stephane AU - Renaud S AD - Department of Thoracic Surgery, Institut Lorrain Du Coeur Et Des Vaisseaux Louis Mathieu, Nancy University Hospital, Nancy, France. FAU - Tian, Hui AU - Tian H AD - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. LA - eng PT - Journal Article PL - China TA - Transl Lung Cancer Res JT - Translational lung cancer research JID - 101646875 PMC - PMC8107730 OTO - NOTNLM OT - Lung adenocarcinoma (LUAD) OT - MAPK/ERK pathway OT - TFIIB-related factor 2 (BRF2) OT - let-7b-3p COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-21-299). The authors have no conflicts of interest to declare. EDAT- 2021/05/21 06:00 MHDA- 2021/05/21 06:01 PMCR- 2021/04/01 CRDT- 2021/05/20 06:44 PHST- 2021/05/20 06:44 [entrez] PHST- 2021/05/21 06:00 [pubmed] PHST- 2021/05/21 06:01 [medline] PHST- 2021/04/01 00:00 [pmc-release] AID - tlcr-10-04-1841 [pii] AID - 10.21037/tlcr-21-299 [doi] PST - ppublish SO - Transl Lung Cancer Res. 2021 Apr;10(4):1841-1856. doi: 10.21037/tlcr-21-299.