4.5 Article

Let-7b-3p inhibits tumor growth and metastasis by targeting the BRF2-mediated MAPK/ERK pathway in human lung adenocarcinoma

期刊

TRANSLATIONAL LUNG CANCER RESEARCH
卷 10, 期 4, 页码 1841-1856

出版社

AME PUBLISHING COMPANY
DOI: 10.21037/tlcr-21-299

关键词

Lung adenocarcinoma (LUAD); let-7b-3p; TFIIB-related factor 2 (BRF2); MAPK; ERK pathway

资金

  1. National Natural Science Foundation of China [81672292]
  2. Taishan Scholar Program of Shandong Province [ts201712087]

向作者/读者索取更多资源

Let-7b-3p, downregulated in lung adenocarcinoma cells and tissues, is associated with poor prognosis in patients. It inhibits proliferation and metastasis of lung adenocarcinoma cells by targeting the BRF2-mediated MAPK/ERK pathway.
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.

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