Abstract
The striatin-interacting phosphatase and kinase (STRIPAK) is the highly conserved complex, which gains increased attention in physiology and pathology process recently. However, limited studies reported the details of STRIPAK complex in cancers while some results strongly suggested it plays a vital role in tumorigenesis. Hence, we systematically analyzed the molecular and survival profiles of 18 STRIPAK genes to assess the value of STRIPAK complex across cancers. Our findings revealed the low frequencies of DNA aberrances and incomparable expression difference of STRIPAK genes between normal and tumor tissues, but they showed strong prognostic value in cancers, especially the liver hepatocellular carcinoma (LIHC) and kidney renal clear cell carcinoma (KIRC). Interestingly, STRIPAK genes were observed the opposite pattern of survival and expression in the above two cancer types. PPP2R1A and TRAF3IP3 were proposed as the oncogenic genes in LIHC and KIRC, respectively. The STRIPAK genes serve as oncogenes may due to the methylation heterogeneity. Taken together, our comprehensive molecular analysis of STRIPAK complex provides resource to facilitate the understanding of mechanism and utilize the potential therapies to tumors.
Highlights
The striatin-interacting phosphatase and kinase (STRIPAK) is a conversed complex during the evolution, which consists of the scaffolding subunit PPP2R1A, catalytic subunit PPP2CA, and regulatory subunit striatins (STRNs) containing STRN, STRN3, and STRN4 (Goudreault et al, 2009; Frost et al, 2012) (Figure 1A and Supplementary Table S1)
Unlike previous researches (Madsen et al, 2015; Chen et al, 2018; Chen R. et al, 2019), which focused on few cancer types, our results revealed that the DNA aberrations, expression and methylation, and prognostic power of STRIPAK complex across over 20 cancer types
PPP2R1A and TRAF3IP3 were identified as the novel potential oncogenic genes through the integrated analysis in liver hepatocellular carcinoma (LIHC) and kidney renal clear cell carcinoma (KIRC), respectively
Summary
The striatin-interacting phosphatase and kinase (STRIPAK) is a conversed complex during the evolution, which consists of the scaffolding subunit PPP2R1A ( known as PP2AA), catalytic subunit PPP2CA ( known as PP2AC), and regulatory subunit striatins (STRNs) containing STRN, STRN3, and STRN4 (Goudreault et al, 2009; Frost et al, 2012) (Figure 1A and Supplementary Table S1). Striatins recruit striatin-interacting protein 1/2 (STRIP1/2, known as FAM40A/B), MOB4, PDCD10 ( known as CCM3). PDCD10 interacts with and stabilizes germinal center kinase III (GCK III) family, which consists of three genes, STK24 ( known as MST3), STK25 ( known as YSK1), and STK26 ( known as MST4) (Fidalgo et al, 2010). The dynamic assembly of STRIPAK complexes regulates the downstream effectors (Chen et al, 2018; Chen R. et al, 2019; Tang et al, 2019)
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