AUTHOR=Chen Quan , Zheng Yiming , Chen Xia , Ge Pengfei , Wang Pengcheng , Wu Bingbing 

TITLE=Upregulation of miR-216a-5p by Lentinan Targeted Inhibition of JAK2/STAT3 Signaling Pathway to Reduce Lung Adenocarcinoma Cell Stemness, Promote Apoptosis, and Slow Down the Lung Adenocarcinoma Mechanisms

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.778096

DOI=10.3389/fonc.2021.778096

ISSN=2234-943X

ABSTRACT=To investigate the effect of Lentinan (LNT) on lung adenocarcinoma (LUAD) cell stemness and its mechanism. Real-time PCR was applied to determine miR-216a-5p expression in human LUAD  tissues and adjacent normal tissues. LNT or miR-216a-5p inhibitor or JAK2/STAT3 signaling pathway agonist IL-6 was used to treat LUAD cell lines H1299 and H460. Proliferation activity, migration and invasion, apoptosis, and stemness of the cells were detected using CCK8, cell colony experiment, Transwell, flow cytometry, and stem cell sphere-forming assay, respectively; the stem cell markers CD90 and CD133, and the related protein expression of JAK2/STAT3 signaling pathway in the cells were identified via Western Blot. Tumorigenesis experiment in vivo in nude mice verified the effect of LNT on LUAD and its molecular mechanism. Compared with the control group, LNT may considerably reduce proliferation, activity, migration, invasion, and stemness of LUAD cells, promote their apoptosis and constrain the volume and weight of tumors in vivo. At the same time, LNT can significantly up-regulate miR-216a-5p levels and reduce p-JAK2/JAK2, p-STAT3/STAT3 levels, thereby inhibiting the JAK2/STAT3 signaling pathway. Interfering with miR-216a-5p expression and activating the JAK2/STAT3 signaling pathway can significantly reverse LNT inhibitory effects on LUAD. Lentinan can inhibit the JAK2/STAT3 signaling pathway by up-regulating miR-216a-5p, reducing stemness, and promoting LUAD cells' apoptosis, then slow down LUAD occurrence and development, providing concepts and experimental foundation treating patients with LUAD.