KHSRP SUMOylation Downregulates The Biogenesis Of Some MiRNAs

MicroRNA(miRNA)and Ago2 form RNA-induced silencing complex(RISC).Complementary base-pairing of the miRNA guides RISC to target messenger RNAs,which are degraded,destabilized or translationally inhibited.miRNAs are important regulatory element of gene expression that control both physiological and pathological processes,including cancers.In the process of miRNAs biogenesis,both Drosha complex and Dicer complex are the most important multiprotein complexes,which exist in nucleus and cytoplasm respectively,in cleavaging precursor miRNAs into mature miRNAs.Post-translational modifications(PTMs)include SUMOyaltion and other modifications.SUMOylation of DGCR8 and TARBP2,which are components of Drosha complex and Dicer complex,regulates miRNAs efficiency in gene-silencing.KHSRP,which is a component of Drosha complex and Dicer complex,promotes the binding between Drosha and pri-miRNAs and upregulates a subset of miRNAs biogenesis.KHSRP is highly expressed in a variety of cancers and is related to both the proliferative and invasive abilities of tumor cells.In present study,we focused on the SUMOylation of KHSRP.Firstly,we identified that KHSRP could be SUMOylated and K87 was the major site of SUMO1 modification.Next,SUMOylation downregulated KHSRP nuclear localization.KHSRP K87 R,de-SUMOylation mutant,promoted a subset of miRNAs biogenesis by increasing its binding with Drosha and pri-miRNAs.At last,the abilities of tumor growth,transformation,differentiation,invasion and migration were increased in shKHSRP tumor cell lines in comparison to shRNA Ctrl.These abilities were downregulated in the tumor cells re-introduced KHSRP K87 R in comparison to KHSRP WT.In conclusion,SUMO1 modification downregulates KHSRP nuclear localization and downregulates its binding with Drosha and pri-miRNAs.In consequence,SUMO1 modification of KHSRP affects a subset of miRNAs biogenesis and is linked to tumorigenesis.