hnRNPK-regulated LINC00263 promotes malignant phenotypes through miR-147a/CAPN2

Abstract Malignant characteristics of cancers, represented by rapid cell proliferation and high metastatic potential, are a major cause cancer-related mortality. As multifunctional RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK) is closely associated with cancer progression in various types cancers. In this study, we sought to identify hnRNPK-regulated long intergenic non-coding RNAs (lincRNAs) that play critical role the regulation malignancy. We found hnRNPK controlled malignant phenotypes including invasiveness, proliferation, clonogenicity. RNA sequencing functional studies revealed LINC00263 , novel target hnRNPK, involved oncogenic functions hnRNPK. Knockdown mitigated capabilities. Conversely, increased were observed -overexpressing cells. Since was mainly localized cytosol highly enriched Argonaute 2-immunoprecipitation (Ago2-IP), hypothesized acts as competitive endogenous (ceRNA), thus -associated microRNAs. Using small followed antisense oligonucleotide pull-down, miR-147a selected for further study. negatively regulates via direct interaction, suppressing Moreover, knockdown upregulated miR-147a, indicating serves ceRNA miR-147a. By analyzing data miRNA prediction, calpain 2 ( CAPN2 ) identified putative Ago2-IP luciferase reporter assay suppressed expression directly binding 3′UTR mRNA. addition, weakened capabilities following or restored inhibition overexpression. Furthermore, our findings validated other cells lung cancer, colorectal neuroblastoma, melanoma. Collectively, demonstrate plays an important malignancy acting decoy upregulating CAPN2.