Gentiana macrophylla flavonoids from Tibetan medicine decreases circ_0059665 to alleviate the progression of non-small cell lung cancer under hypoxia.

BACKGROUND: Gentiana macrophylla Pall. is a traditional Tibetan medicinal herb possessing antinociceptive and anti-inflammatory activities. Circular RNAs (circRNAs) have been identified to be involved in the tumorigenesis of non-small cell lung cancer (NSCLC). Here, this study focused on investigating the function and mechanism of Gentiana macrophylla flavonoids (GF) and circ_0059665 in NSCLC progression. METHODS: The contents of mRNA and protein were detected using qRT-PCR and western blotting analysis. Cell proliferative and invasive abilities were evaluated by cell counting kit-8, EdU, colony formation and transwell assays, respectively. M2 macrophage polarization was analyzed by flow cytometry. RESULTS: GF treatment suppressed NSCLC cell proliferation, invasion and M2 macrophage polarization under hypoxic conditions. Circ_0059665 was highly expressed in NSCLC tissues and cells. Its expression was increased under hypoxic conditions but was reduced following GF treatment. Furthermore, circ_0059665 overexpression reversed the anticancer effects of GF on NSCLC cells under hypoxic conditions. Mechanistically, circ_0059665 acted as a sponge for miR-512-5p to regulate NOVA2 expression. Hypoxia decreased miR-512-5p levels, and increased NOVA2 levels in NSCLC cells, while these tendencies were abolished after GF treatment. Circ_0059665 silencing inhibited NSCLC cell proliferation, invasion and M2 macrophage polarization in hypoxic environments, which were counteracted by NOVA2 overexpression. Moreover, NOVA2 upregulation reversed the suppressive effects of GF on NSCLC cells with hypoxia treatment. In addition, GF impeded NSCLC tumor growth in vivo via suppressing circ_0059665. CONCLUSION: GF treatment in hypoxic environments suppressed NSCLC cell proliferation, invasion and M2 macrophage polarization via the circ_0059665/miR-512-5p/NOVA2 axis.

Salidroside suppresses the multiple oncogenic activates and immune escape of lung adenocarcinoma through the circ_0009624-mediated PD-L1 pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) is a fatal malignancy all over the world. Salidroside (SAL) is an active component extracted from Rhodiola rosea that has been reported to exert antitumor activity against several human cancers, containing lung adenocarcinoma (LUAD). The purpose of this study was to explore the effect and underlying mechanism of SAL in LUAD. METHODS: Cell viability, proliferation, migration, and invasion were measured using cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and transwell assays. Effects of LUAD cells on the cytotoxicity, percentage, and death of CD8+ cells were detected using lactate dehydrogenase (LDH) and flow cytometry assays. Programmed cell death ligand 1 (PD-L1) protein level was examined using western blot. Circ_0009624, enolase 1 (ENO1), and PD-L1 levels were determined using real-time quantitative polymerase chain reaction (RT-qPCR). The biological role of SAL on LUAD tumor growth was assessed using the xenograft tumor model in vivo. RESULTS: SAL restrained LUAD cell proliferation, migration, invasion, and immune escape in vitro via modulating PD-L1. Circ_0009624 expression was increased in LUAD. Applying SAL repressed circ_0009624 and PD-L1 expression in LUAD cells. SAL treatment hindered suppressed various oncogenic activates and immune escape of LUAD cells by regulating the circ_0009624/PD-L1 pathway. SAL blocked LUAD xenograft growth in vivo. CONCLUSION: Applying SAL might constrain malignant phenotypes and immune escape of LUAD cells partially through the circ_0009624-mediated PD-L1 pathway, providing a novel insight for LUAD treatment.