Abstract
Little is known about the function of Keratin 80 (KRT80), an epithelial keratin, in cancer. This study investigated the role of KRT80 in the prognosis of colorectal carcinoma (CRC) and the underlying mechanisms involved in CRC migration and invasion. We analyzed the expression of KRT80 using The Cancer Genome Atlas and Oncomine databases. Higher expression of KRT80 was found to be significantly associated with multiple pathological parameters, lower disease-free survival, and overall survival in CRC patients. Also, KRT80 was an independent prognostic indicator for CRC. Furthermore, altered KRT80 expression impacted migration and invasion of CRC cells, as well as the expression of epithelial–mesenchymal transition (EMT)-related markers and cell morphology via the AKT pathway. Inhibiting the expression of AKT could reverse these phenomena. Liquid Chromatograph Mass Spectrometer/Mass Spectromete, Co-immunoprecipitation, and laser scanning confocal microscopy techniques showed that KRT80 could interact with protein kinase, DNA-activated, catalytic polypeptide (PRKDC). Suppressing PRKDC could inhibit the expression of AKT and EMT, as well as the migration and invasion of CRC cells. Taken together, these results demonstrated that KRT80 was an independent prognostic biomarker for CRC and promoted CRC migration and invasion by interacting with PRKDC via activation of the AKT pathway.
Highlights
Prominent advances have been made in the treatment of colorectal carcinoma (CRC), it remains the most common gastrointestinal cancer worldwide, with high morbidity and mortality rates[1]
Using Liquid Chromatograph Mass Spectrometer/Mass Spectrometer (LC-MS/MS), Co-immunoprecipitation (Co-IP), and laser scanning confocal microscopy (LSCM), we demonstrated that Keratin 80 (KRT80) interacted with Protein Kinase, DNA-Activated, Catalytic Polypeptide (PRKDC), called as DNA-Dependent Protein Kinase Catalytic Subunit in CRC
KRT80 is upregulated in human CRC tissues The keratin family type II RNA expression was examined in the The Cancer Genome Atlas (TCGA) and Oncomine databases
Summary
Prominent advances have been made in the treatment of colorectal carcinoma (CRC), it remains the most common gastrointestinal cancer worldwide, with high morbidity and mortality rates[1]. Around 25% of newly diagnosed patients with CRC have metastasis, whereas ~ 50% of patients with localized tumors will eventually develop metastasis, with most of these tumors being unresectable[2]. The available clinical biomarkers have unsatisfactory sensitivity and specificity for CRC prognostic evaluation[3]. Identifying specific altered genes and/or biomarkers with high sensitivity and specificity will be invaluable for early diagnosis and prognosis of CRC. Keratins are intermediate filament cytoskeletal proteins of epithelial cells that are responsible for their structural integrity[4]. Keratins can be divided into two types: acidic or type I and basic or neural type II.
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