Piperlongumine inhibits the growth of non-small cell lung cancer cells via the miR-34b-3p/TGFBR1 pathway.

BACKGROUND: Non-small cell lung cancer is a common type of lung cancer. Piperlongumine (PL), which is extracted from the roots of piperaceae plant, long pepper, and peppercorn, is an alkaloid amide that inhibits tumor growth and metastasis. However, whether it affects lung cancer cells remains unclear. METHODS: We assessed the effects of PL on the proliferation and apoptosis of A549 and H1299 NSCLC cell lines. RESULTS: PL was mildly toxic to normal human bronchial epithelial cells and significantly suppressed growth and facilitated apoptosis of A549 and H1299 cells. It also upregulated microRNA (miR)-34b-3p and downregulated the transforming growth factor beta type I receptor (TGFBR1). The dual-luciferase reporter assay showed that TGFBR1 is a target gene of miR-34b-3p. Silencing of miR-34b-3p or overexpression of TGFBR1 partially attenuated the effects of PL on A549 and H1299 cells. CONCLUSIONS: PL inhibits proliferation and induces apoptosis of A549 and H1299 cells by upregulating miR-34b-3p and modulating TGFBR1 signaling pathway.

Downregulation of LINC00665 confers decreased cell proliferation and invasion via the miR-138-5p/E2F3 signaling pathway in NSCLC.

Non-small cell lung cancer (NSCLC) is a type of malignant tumor which threatens human health and life. Recently, some researches on long non-coding RNAs (lncRNAs) in NSCLC has elucidated critical regulatory roles in cell proliferation, migration, and invasion, the relative clinical significance and mechanisms of action are still unclear. This study focuses on the important role of a novel lncRNA LINC00665 in the development of NSCLC. Long intergenic non-protein coding RNA 665 gene (LINC00665) was found through microarray analysis and was measured by real-time quantitative PCR (RT-qPCR). The interactions between LINC00665 and miR-138-5p as well as the interactions between miR-138-5p and E2F3 (E2F transcription factor 3) were explored by bioinformatics analysis and dual-luciferase assays. CCK-8, transwell and mouse xenograft assays were performed to investigate the effects of LINC00665 and miR-138-5p on NSCLC proliferation and invasion. As a result, LINC00665 expression was upregulated in NSCLC lung tissues and cells. Downregulated LINC00665 could arrest A549 and H1299 cell proliferation and invasion in vitro, and this finding was recapitulated in vivo. LINC00665 directly regulated the expression of miR-138-5p. Additionally, E2F3 was one of the targets of miR-138-5p; E2F3 without 3'UTR could reverse the inhibitory effects of downregulated LINC00665 on proliferation and invasion in A549 and H1299 cells. In conclusion, dysregulation of LINC00665 plays a vital role in NSCLC progression, indicating that its downregulation may confer decreased cell proliferation and invasion via the miR-138-5p/E2F3 signaling pathway.