CircRNA ZKSCAN1 promotes lung adenocarcinoma progression by miR-185-5p/TAGLN2 axis

Abstract

Background: Circ-ZKSCAN1 has been found to accelerate non-small cell lung cancer (NSCLC) progression; however, the role and mechanism of circ-ZKSCAN1 in lung adenocarcinoma (LUAD) cisplatin (DDP) resistance remain unclear.

Methods: Levels of genes and proteins were examined using qRT-PCR. Functional experiments were performed using CCK-8 assay, flow cytometry, transwell assay and xenograft model assay, respectively. Glucose metabolism was calculated by detecting glucose consumption, lactate production, ATP and HK-2 levels. The interaction between miR-185-5p and circ-ZKSCAN1 or transgelin 2 (TAGLN2) was validated by dual-luciferase reporter assay.

Results: Circ-ZKSCAN1 was highly expressed in DDP-resistant LUAD tissues and cell lines, and circ-ZKSCAN1 knockdown weakened DDP resistance and suppressed cell viability, migration, invasion, and glycolysis in LUAD. Circ-ZKSCAN1 acted as a sponge of miR-185-5p, and the regulatory effects of circ-ZKSCAN1 knockdown on LUAD were reversed by miR-185-5p downregulation. Meanwhile, miR-185-5p directly targeted TAGLN2, and performed anticancer effects by regulating TAGLN2. Importantly, silencing of circ-ZKSCAN1 hindered tumor growth and promoted DDP sensitivity in vivo via regulating miR-185-5p and TAGLN2.

Conclusion: Circ-ZKSCAN1 promoted LUAD tumorigenesis and DDP resistance by regulating miR-185-5p/TAGLN2 axis.

Keywords: LUAD; TAGLN2; circ-ZKSCAN1; cisplatin resistance; miR-185-5p.