Abstract
Human KHDRBS1/Sam68 is an oncogenic splicing factor involved in signal transduction and pre-mRNA splicing. We explored the molecular mechanism of KHDRBS1 to be a prognostic marker in four different cancers. Within specific cancer, including kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), acute myeloid leukemia (LAML), and ovarian cancer (OV), KHDRBS1 expression is heterogeneous and patient specific. In KIRP and LUAD, higher expression of KHDRBS1 affects the patient survival, but not in LAML and OV. Genome-wide coexpression analysis reveals genes and transcripts which are coexpressed with KHDRBS1 in KIRP and LUAD, form the functional modules which are majorly involved in cancer-specific events. However, in case of LAML and OV, such modules are absent. Irrespective of the higher expression of KHDRBS1, the significant divergence of its biological roles and prognostic value is due to its cancer-specific interaction partners and correlation networks. We conclude that rewiring of KHDRBS1 interactions in cancer is directly associated with patient prognosis.
Highlights
Human KHDRBS1 (KH domain-containing, RNA-binding, signal transduction-associated protein 1) gene encodes Sam[68] (Src substrate associated in mitosis 68 kDa), a member of STAR family of RNA-binding proteins[1,2]
Higher and lower expression is classified based on the Z-score value of KHDRBS1 expression, which is provided by the cancer genome atlas (TCGA) for all four cancer types i.e. kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), ovarian cancer (OV) and LAML
We evaluated the expression level of KHDRBS1 in KIRP, LUAD, LAML and OV cancer
Summary
Human KHDRBS1 (KH domain-containing, RNA-binding, signal transduction-associated protein 1) gene encodes Sam[68] (Src substrate associated in mitosis 68 kDa), a member of STAR (signal transduction activator of RNA) family of RNA-binding proteins[1,2]. Higher expression of Sam68/KHDRBS1 is shown to play significant role in various cancer cells, such as, colon[9], prostate[10], renal[11], colorectal[12], breast[13], esophageal squamous cell carcinoma[6] neuroblastoma[14] bladder cancer[15] renal cell carcinoma[11], cervical cancer[7] hepatic cancer[16] and non-small lung cancer cells[17] It is identified as a prognostic marker in a few cancer tissues[11,15]. Our finding suggests that the clinical outcomes of higher expression of KHDRBS1 depend on context-specific molecular interaction network which could be an essential parameter to design personalized medicine
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