ETV4 mediated lncRNA C2CD4D-AS1 overexpression contributes to the malignant phenotype of lung adenocarcinoma cells via miR-3681-3p/NEK2 axis.

Lung adenocarcinoma (LUAD) is originated from the mucus-producing glands of the lungs. The involvement of long noncoding RNAs (lncRNAs) has been discovered in multiple diseases. In the present research, we aimed to unmask the role of C2CD4D and THEM5 antisense RNA 1 (C2CD4D-AS1) in LUAD. RT-qPCR or western blot analysis was respectively applied in the detection of RNA or protein expressions. The function of C2CD4D-AS1 in LUAD was assessed by functional assays. Through ChIP, RNA pull down, DNA pull down, RIP and luciferase reporter assays, the in-depth regulatory mechanism of C2CD4D-AS1 in LUAD was explored. C2CD4D-AS1 was dramatically overexpressed in LUAD tissues and cell lines. As a result, depletion of C2CD4D-AS1 significantly repressed cell proliferation, migration, invasion and stimulated cell apoptosis in LUAD. Mechanistically, ETS variant transcription factor 4 (ETV4) activated the transcription of C2CD4D-AS1 and stimulated its up-regulation in LUAD cells, thus affecting LUAD cell biological functions. Furthermore, C2CD4D-AS1 sponged microRNA-3681-3p (miR-3681-3p) and regulated NIMA-related kinase 2 (NEK2), thus participating in modulating LUAD cell biological behaviors. To conclude, C2CD4D-AS1 up-regulation induced by ETV4 enhanced NEK2 expression by sequestering miR-3681-3p to contribute to the malignant behaviors of LUAD cells.