Abstract
BackgroundNon-small cell lung cancer (NSCLC) is a leading threat to human lives with high incidence and mortality. Circular RNAs were reported to play important roles in human cancers. The purpose of this study was to investigate the role of circ_0005962 and explore the underlying functional mechanisms.MethodsThe protein levels of Beclin 1, light chain3 (LC3-II/LC3-I), Pyruvate dehydrogenase kinase 4 (PDK4), Cleaved Caspase 3 (C-caspase 3), and proliferating cell nuclear antigen were examined using western blot analysis. Glycolysis was determined according to the levels of glucose consumption and lactate production. Xenograft model was constructed to investigate the role of circ_0005962 in vivo.Resultcirc_0005962 expressed with a high level in NSCLC tissues and cells. circ_0005962 knockdown inhibited proliferation, autophagy, and glycolysis but promoted apoptosis in NSCLC cells. miR-382-5p was targeted by circ_0005962, and its inhibition reversed the role of circ_0005962 knockdown. Besides, PDK4, a target of miR-382-5p, was regulated by circ_0005962 through miR-382-5p, and its overexpression abolished the effects of miR-382-5p reintroduction. circ_0005962 knockdown suppressed tumor growth in vivo.Conclusioncirc_0005962 knockdown restrained cell proliferation, autophagy, and glycolysis but stimulated apoptosis through modulating the circ_0005962/miR-382-5p/PDK4 axis. Our study broadened the insights into understanding the mechanism of NSCLC progression.
Highlights
Lung cancer is a leading cause of cancer-related death worldwide [1]
The survival curve was depicted utilizing Kaplan–Meier survival rate analysis according to the living status of Non-small cell lung cancer (NSCLC) patients, and we found that the survival rate of patients with high expression of circ_0005962 was notably weaker compared with patients with low circ_0005962 expression (Figure 1c)
The level of lactate production inhibited in the si-circ_0005962#1 group was largely promoted in the si-circ_0005962#1 + anti-miR382-5p group (Figure 4g). These results indicated that circ_0005962 knockdown inhibited proliferation, autophagy, and glycolysis but induced apoptosis by enhancing the expression of miR-382-5p
Summary
Lung cancer is a leading cause of cancer-related death worldwide [1]. Lung cancer is the second most common cancer among men and women: second only to prostate cancer in men, and second only to breast cancer in women [2]. Non-small cell lung cancer (NSCLC) and small cell lung cancer are two types of lung cancer, and NSCLC accounts for about 85% of all lung cancer cases [3]. NSCLC, including large cell carcinoma, squamous cell carcinoma, and adenocarcinoma, is associated with high incidence and mortality [4,5]. Treatment modalities, including chemotherapy and surgery, are used to treat NSCLC, but the 5-year overall survival rate for all stages of NSCLC patients is only 16% [2,6]. The severe situation of NSCLC treatment makes it urgent to further explore the mechanism of occurrence and development of NSCLC to establish novel therapeutic strategies
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