Circ_SEC61A1 contributes to the progression of multiple myeloma cells via regulating miR-660-5p/CDK6 axis

Background: Circular RNAs (circRNAs) have been reported to play critical roles in the malignant progression of diverse human cancers, including multiple myeloma (MM). This study aimed to explore the functional role and underlying mechanism of circ_SEC61A1 in MM progression.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to detect the expression levels of circ_SEC61A1, microRNA (miR)-660-5p and cyclin-dependent kinase 6 (CDK6) mRNA. The localization of circ_SEC61A1 in MM cells was tested by the subcellular fractionation location assay. Actinomycin D assay was conducted to determine the characteristics of circ_SEC61A1. Cell proliferation was evaluated by colony formation assay, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay and 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Western blot assay was exploited to examine the expression of proteins. Cell migration and invasion were tested via transwell assay, and cell apoptosis was measured by flow cytometry analysis. Dual-luciferase reporter assay was utilized to confirm the interaction between miR-660-5p and circ_SEC61A1 or CDK6.

Results: Circ_SEC61A1 level was increased in MM tissues and cells. Circ_SEC61A1 was a stable circRNA and mainly located in cytoplasm. Circ_SEC61A1 silence restrained the proliferation, metastasis and expedited the apoptosis in MM cells. CDK6 was identified as the target of miR-660-5p, and circ_SEC61A1 sponged miR-660-5p to positively regulate CDK6 expression. The inhibitory impacts of circ_SEC61A1 knockdown on the progression of MM cells were mitigated by miR-660-5p inhibition. MiR-660-5p overexpression blocked the malignant phenotypes of MM cells by targeting CDK6.

Conclusion: Our study manifested that circ_SEC61A1 could accelerate MM progression at least partially through modulating miR-660-5p/CDK6 axis.