[No authors listed]
The molecular and clinical heterogeneity in diffuse large Bâcell lymphoma (DLBCL) has raised a need for the investigation of potential therapeutic biomarkers. MicroRNAâ320 (miRâ320) and CDK6 are both involved in the regulation of cell proliferation in various types of cancer. To investigate the clinical role of CDK6 in DLBCL, CDK6 expression was assessed using immunohistochemistry on formalinâfixed, paraffinâembedded sections. Furthermore, to investigate the relationship between CDK6 and miRâ320d, as well as their roles in cell proliferation, a series of experimentally functional validations was performed in DLBCL cell lines. Bioinformatics software and DualâLuciferase reporter assay were used to predict and validate the potential target of miRâ320d. In DLBCL cells transfected with miRâ320d lentiviral vector, CDK6 expression at the protein and mRNA levels was detected using western blotting and qRTâPCR, respectively. Overexpression and smallâhairpin RNA knockdown of CDK6 were performed by lentiviral transduction. The results of these experiments revealed that CDK6 was overexpressed and predictive of poor prognosis in DLBCL patients. Moreover, CDK6 was revealed to be directly targeted by miRâ320d and either overexpression of miRâ320d or knockdown of CDK6 inhibited proliferation. In conclusion, CDK6 overexpression in DLBCL may result from miRNAâ320d downregulation and subsequent loss of inhibition of cell proliferation, suggesting that miRNAâ320d may be a potential therapeutic target for the treatment of DLBCL with high CDK6 expression.
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