KRT84 is a potential tumor suppressor and good prognosis signature of oral squamous cell carcinoma

Abstract

Aims: Oral squamous cell carcinoma (OSCC) is a common oral cancer; however, current therapeutic approaches still show limited efficacy. Our research aims to explore effective biomarkers related to OSCC. Main methods: Gene expression profiles of paired OSCC tumor and paracancerous samples from The Cancer Genome Atlas (TCGA) were analyzed. mRNA and protein levels of KRT84 in OSCC cell line HSC-3 were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. KRT84 protein levels in OSCC tumor samples of different stages were determined by immunohistochemistry. Overall survival (OS) of OSCC samples was evaluated and association of multiple factors with OS was assessed. Key findings: Compared with paracancerous samples, 4642 DEGs were identified in OSCC tumor samples. Among them, KRT84 expression level in OSCC tumor tissues was obviously decreased, which was validated in HSC-3 cells. KRT84 expression level showed decreasing tendency with the increase of tumor grade and stage. Patients with low KRT84 expression level had inferior OS independently of multiple factors. Besides, antigen processing and presentation pathway were significantly activated in OSCC samples with high KRT84 expression. Elevated KRT84 mRNA as well as protein levels were confirmed by RT-qPCR and Western blot in OSCC and normal cell lines, and immunohistochemistry in OSCC tumor and paracancerous tissues. Significance: Our study suggests KRT84 as a tumor suppressor and good prognostic indicator for OSCC, which might be significant for OSCC diagnosis and treatment.

E3 ubiquitin ligase RNF187 promotes growth of spermatogonia via lysine 48‐linked polyubiquitination‐mediated degradation of KRT36/KRT84

“…23 KRT84 has been reported to be a potential oncogene in oral squamous cell carcinoma. 29 In the present study, accompanied by a downregulation of Notch signaling pathway-related genes in RNF187 and KRT36/KRT84 co-overexpression group compared with RNF187 overexpression alone, GC-1 cell proliferation and migration were also attenuated in RNF187 and KRT36/KRT84 co-overexpression group. These findings demonstrate that RNF187 promotes the Notch signaling pathway by downregulating KRT36 and KRT84.…”

“…Silencing of KRT19 has also been reported to lead to proliferation and migration of breast cancer cells via the upregulated Notch signaling pathway 23 . KRT84 has been reported to be a potential oncogene in oral squamous cell carcinoma 29 . In the present study, accompanied by a downregulation of Notch signaling pathway‐related genes in RNF187 and KRT36/KRT84 co‐overexpression group compared with RNF187 overexpression alone, GC‐1 cell proliferation and migration were also attenuated in RNF187 and KRT36/KRT84 co‐overexpression group.…”

“…28 In oral squamous cell carcinoma, KRT84 was downregulated and decreased with increasing tumor grade. 29 In this study, we explored the detailed molecular mechanisms of RNF187 expression and function in spermatogonia. We found that RNF187 participates in the regulation of spermatogonia growth via K48-linked polyubiquitinationmediated degradation of KRT36/KRT84.…”

“…OTUB2, a deubiquitinase, regulated the stability of KRT80 by deubiquitination and then promoted gastric cancer cell proliferation by activating the Akt signaling pathway 28 . In oral squamous cell carcinoma, KRT84 was downregulated and decreased with increasing tumor grade 29 …”