Abstract
BackgroundLung cancer (LC) is a malignant tumor originating in the bronchial mucosa or gland of the lung. Circular RNAs (circRNAs) are proved to be key regulators of tumor progression. However, the regulatory effect of circ_0001421 on lung cancer tumorigenesis remains unclear.MethodsThe expression levels of circ_0001421, microRNA-4677-3p (miR-4677-3p) and cell division cycle associated 3 (CDCA3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Methyl thiazolyl tetrazolium (MTT), Transwell and Tumor formation assays were performed to explore the role of circ_0001421 in LC. Glucose consumption and lactate production were examined by a Glucose assay kit and a Lactic Acid assay kit. Western blot was utilized to examine the protein levels of Hexokinase 2 (HK2) and CDCA3. The interaction between miR-4677-3p and circ_0001421 or CDCA3 was confirmed by dual-luciferase reporter assay.ResultsCirc_0001421 was increased in LC tissues and cells, and knockdown of circ_0001421 repressed cell proliferation, migration, invasion and glycolysis in vitro. Meanwhile, circ_0001421 knockdown inhibited LC tumor growth in vivo. Mechanistically, circ_0001421 could bind to miR-4677-3p, and CDCA3 was a target of miR-4677-3p. Rescue assays manifested that silencing miR-4677-3p or CDCA3 overexpression reversed circ_0001421 knockdown-mediated suppression on cell proliferation, migration, invasion and glycolysis in LC cells.ConclusionCirc_0001421 promoted cell proliferation, migration, invasion and glycolysis in LC by regulating the miR-4677-3p/CDCA3 axis, which providing a new mechanism for LC tumor progression.
Highlights
Lung cancer (LC) is a malignant tumor originating in the bronchial mucosa or gland of the lung
cell division cycle associated 3 (CDCA3) overexpression reversed the inhibitory effects of circ_0001421 knockdown on LC cell proliferation, migration, invasion and glycolysis Considering that circ_0001421 could regulate the expression of CDCA3, we investigated whether circ_0001421 played a role in LC cells by regulating CDCA3
We demonstrated that circ_0001421 knockdown impeded cell proliferation (Fig. 6b), migration (Fig. 6c) and invasion (Fig. 6d), all of which could be neutralized by overexpression of CDCA3 in A549 and H1299 cells
Summary
Lung cancer (LC) is a malignant tumor originating in the bronchial mucosa or gland of the lung. Circular RNAs (circRNAs) are proved to be key regulators of tumor progression. The regulatory effect of circ_0001421 on lung cancer tumorigenesis remains unclear. Lung cancer (LC) is a malignant tumor with the highest morbidity and mortality in worldwide [1, 2]. The 5year survival rate of LC patients is only 17.7%, mainly on account of the rapid tumor metastasis and local recurrence [3]. The 5-year survival rate of patients with. Circular RNA (circRNA) is a special form of non-coding RNA (ncRNA) that form a loop with jointed 3′ heads and 5′ tails [5]. A number of circRNAs were involved in cancer
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