Circ-RBMS1 Knockdown Alleviates CSE-Induced Apoptosis, Inflammation and Oxidative Stress via Up-Regulating FBXO11 Through miR-197-3p in 16HBE Cells

Abstract

Background: Emerging evidence has reported that circular RNAs (circRNAs) are aberrantly expressed and act as significant regulators in pathological processes of chronic obstructive pulmonary disease (COPD). Here, the purpose of this article was to evaluate and clarify the biological functions and mechanism of circRNA single stranded interacting protein 1 (circ-RBMS1) in cigarette smoke (CS)-induced COPD. Methods: Human bronchial epithelial cells 16HBE treated with or without cigarette smoke extract (CSE) were used in the experimental group in vitro. Levels of circ-RBMS1, microRNA (miR)-197-3p, and F-box only protein 11 (FBXO11) were detected using quantitative real-time polymerase chain reaction and Western blot. The present study used cell counting kit-8 (CCK-8), 5-ethynyl-2ʹ-deoxyuridine (EDU), flow cytometry and Western blot assays to determine the survival of 16HBE cells. The activity of interleukin (IL)-1β, tumor necrosis factor (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) was evaluated using the relative commercial kits. Dual-luciferase activity and RIP assays were used to identify the target relationship between miR-197-3p and circ-RBMS1 or FBXO11. Results: Circ-RBMS1 was highly expressed in COPD patients, and CSE induced an increased expression of circ-RBMS1 in a dose-dependent manner. Functionally, knockdown of circ-RBMS1 attenuated CSE-induced apoptosis, inflammation and oxidative stress in 16HBE cells. Circ-RBMS1 directly targeted miR-197-3p, and miR-197-3p inhibition reversed the effects of circ-RBMS1 knockdown on CSE-induced 16HBE cells. FBXO11 was a target of overexpression or FBXO11 silencing reduced the apoptosis, inflammation and oxidative stress in CSE-induced 16HBE cells. Moreover, miR-197-3p exerted its effects by targeting FBXO11. Additionally, circ-RBMS1 acted as a sponge for miR-197-3p to positively regulate FBXO11 expression in 16HBE cells. Conclusion: Circ-RBMS1 knockdown alleviated CSE-induced apoptosis, inflammation and oxidative stress in 16HBE cells via miR-197-3p/FBXO11 axis, suggesting a new insight into the pathogenesis of CS-induced COPD.

Knockout of circRNA single stranded interacting protein 1 (circRBMS1) played a protective role in myocardial ischemia-reperfusion injury though inhibition of miR-2355-3p/Mammalian Sterile20-like kinase 1 (MST1) axis

“…A previous study found circRBMS1 expression was increased in patients with chronic obstructive pulmonary disease. The in vitro study further illustrated that inhibition of circ-RBMS1 attenuated cell apoptosis, inflammatory response and oxidative stress in 16HBE cells exposed to cigarette smoke [ 10 ]. Our findings also suggested circRBMS1 served as a sponge for miR-2355-3p in HCMs.…”

“…Circular RNA ciRS‐7 (ciRS-7) is reported to suppress cell proliferation, invasion, and tube formation as well as promote cell apoptosis through sponging miR-26a-5p via PI3K/AKT and JNK/p38 signaling pathways in human microvascular endothelia, indicating the function of ciRS-7 in miocardial infarction [ 9 ]. Interesting, a previous study reports circRBMS1 mediates cell apoptosis, inflammation, and oxidative stress in chronic obstructive pulmonary disease [ 10 ]. Close association is found between miR-2355-3p and various diseases, such as diabetic nephropathy [ 11 ], pancreatic cancer [ 12 ] and heart failure [ 13 ].…”

Context-Dependent Regulation of Gene Expression by Non-Canonical Small RNAs

“…FBXO11 promotes the degradation of proteins critical in regulation of the cell cycle, such as BCL6, SNAIL and p53. Therefore, by acting as a sponge for miR-197-3p, circ-RBMS1 positively regulates FBXO11 expression in bronchial epithelial cells, enhancing CSE-induced apoptosis, inflammation, and oxidative stress [ 109 , 110 ].…”

Effect of glaucocalyxin B on the protein expressions of PTEN, Beclin1 and LC3 in a mouse model of transplanted cervical cancer, and its significance

“…Glaucocalyxin B (GLB) is a TCM compound extracted from Blue calyx. It has been reported that GLB inhibited the growths of tongue squamous cell carcinoma, breast cancer and other malignant tumors, although there are limited studies on its effect on cervical cancer [5]. In this study, the effects of GLB on protein expressions of PTEN, Beclin-1 and LC3 were determined in a female mouse model of BALB/C cervical cancer graft.…”