Circ_0001421 facilitates glycolysis and lung cancer development by regulating miR-4677-3p/CDCA3

Abstract

Background 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. However, the regulatory effect of circ_0001421 on lung cancer tumorigenesis remains unclear. Methods The 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. Results Circ_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. Conclusion Circ_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.

Pan-cancer analysis identifies CDCA3 as a novel prognostic marker associated with immune infiltration in lung adenocarcinoma through bioinformatics analysis

“…The clinical application of immunotherapy has shifted the focus of tumor treatment from tumor cells to the tumor microenvironment (27). Based on CIBERSORT bioinformatics analysis, our study found that 14 of 22 types of immune cells had significant differences in the high and low CDCA3 expression groups, including memory B cells, activated mast cells (P<0.05), follicular helper T cells, 4677-3p/CDCA3 axis is a ceRNA network that boosts proliferation and migration in HCC, BC, and LC (21,30,31). LncRNA LINC00707 accelerates the development and progression of BC by targeting miR-145/CDCA3 (22).…”

Identification of lncRNA, miRNA and mRNA expression profiles and ceRNA Networks in small cell lung cancer

“…Furthermore, CDCA3, which encodes cell division cycle associated protein-3, is also found to be increased in NSCLC tissues and associated with poor patient prognosis [ 27 ]. Zhang et al reported that CDCA3 is regulated by miR-4677-3p during lung cancer development [ 60 ]. Four other genes involved in the ceRNA network, including MCM7 [ 29 ], NCAPG2 [ 31 ], SETD6 [ 34 ], and KIF22 [ 35 ] have also been reported to involved in lung cancer progression.…”

CircZDBF2 up-regulates RNF145 by ceRNA model and recruits CEBPB to accelerate oral squamous cell carcinoma progression via NFκB signaling pathway

“…This circRNA-miRNA-mRNA regulatory axis has been identified in a variety of human cancer cells [20]. For instance, circ_0001421 promotes glycolysis and lung cancer development by regulating miR-4677-3p to upregulating cell division cycle associated 3 (CDCA3) [37]. Circ_0084927 sponges miR-142-3p and up-regulates ADP ribosylation factor like GTPase 2 (ARL2) to aggravate the proliferation of cervical cancer cells [38].…”