Circ-NUP98 Promotes Lung Adenocarcinoma Development Through Regulating CBX1 by miR-188-3p.

Abstract

Lung cancer has a high morbidity and mortality among malignant tumors, and lung adenocarcinoma (LUAD) is the main type of lung cancer. In recent years, circular RNAs (circRNAs) have been confirmed to play an important role in the generation and development of human cancer. However, the specific role and mechanism of circ-NUP98 in LUAD are still unclear and need to be further investigated. Circ-NUP98, microRNA-188-3p (miR-188-3p), and chromobox homolog 1 (CBX1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell-counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, wound healing, and transwell assay were used to observe LUAD cell proliferation, apoptosis, migration, invasion, and cell-cycle progression. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were examined using special assay kits. CyclinD1, Bcl-2-related X protein (Bax), matrix metalloproteinase 9 (MMP9) protein, and CBX1 protein levels were determined using Western blot. The interaction between miR-188-3p and circ-NUP98 or CBX1 was identified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assay. In vivo efficacy of circ-NUP98 was evaluated in a xenograft tumor model. Besides, the expression of CBX1 and KI67 in the tumors was detected by immunohistochemical (IHC) assay. Circ-NUP98 and CBX1 expressions were upregulated in LUAD tissues and cells, and miR-188-3p was decreased. Downregulation of circ-NUP98 could inhibit the proliferation, migration, invasion, and oxidative stress, and promote apoptosis of LUAD cells. Mechanism experiments showed that circ-NUP98 acted as a sponge for miR-188-3p to increase CBX1 expression. Knockdown of circ-NUP98 could inhibit the growth of LUAD tumors in vivo. Circ-NUP98 might promote the malignant development of LUAD via the miR-188-3p/CBX1 axis, which might provide a potential new marker for early diagnosis of LUAD.