Expression ofSESN1, UHRF1BP1, and miR-377-3p as prognostic markers in mutatedTP53squamous cell carcinoma of the head and neck

Abstract

The tumor suppressor gene TP53 is the most frequently mutated gene in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). It represents a known transcription factor that controls different microRNAs (miRNA) and target genes involved in the regulation of cellular stress, apoptosis and response to DNA damage. We used The Cancer Genome Atlas database to investigate the difference in transcriptome and proteome levels between mutated and wild-type TP53 HPV-negative HNSCC. Using different databases and an extensive literature review, we built the transcriptional and post-transcriptional network regulated by TP53. TP53 mutation was associated with poor overall survival in 203 HPV-negative patients compared to 40 patients with TP53 wild-type tumors. Using the enrichment analysis, we found that UHRF1BP1 and SESN1 mRNA were linked to prognosis in the TP53 mutated group. This is also the case for miR-377-3p, an important miRNA regulator of SESN1. Our study shows that SESN1 mRNA, UHRF1BP11 mRNA and miRNA-377-3p levels are prognostically relevant in HPV-negative HNSCC patients. This finding may help with patient stratification and the development of potential new therapeutic targets to treat patients with HNSCC.

Mouse bone marrow mesenchymal stem cells with distinct p53 statuses display differential characteristics

“…To determine whether the above miRNAs were regulated by p53, the differential expression of these mirnas in p53 +/+ , p53 +/and p53 -/-mBM-MScs was investigated. The results revealed that mir-3152 and mir-377 were highly expressed in p53 +/and p53 -/-mBM-MScs, which is consistent with their expression levels in other types of cancer (28)(29)(30)(31)(32) and suggested that they served an oncogenic role following p53 inactivation. conversely, mir-221, mir-155 and mir-4669 expression levels were observed to be decreased in p53 +/and p53 -/-mBM-MSCs, which based on previous studies (32)(33)(34)(35)(36)(37)(38)(39), suggested that they may serve a tumor suppressive role in MSCs.…”

“…Moreover, mir-3152 is involved in the therapeutic response to neoadjuvant radio-chemotherapy resistance observed in squamous cell carcinoma of esophagus (eScc), which suggested that miR-3152 could act as a predictive biomarker for pre-therapeutic patient selection (28). mir-377 drives malignant characteristics and acts as a prognostic biomarker in multiple different cancers (29)(30)(31)(32), whereas mir-221 is involved in osteosarcoma and Gc progression (33,34). mir-155 has previously been observed to regulate melanoma cell growth by acting as a tumor suppressor (35), and it is overexpressed in hematological malignancies and solid tumors (36).…”

“…conversely, mir-221, mir-155 and mir-4669 expression levels were observed to be decreased in p53 +/and p53 -/-mBM-MSCs, which based on previous studies (32)(33)(34)(35)(36)(37)(38)(39), suggested that they may serve a tumor suppressive role in MSCs. In fact, p53 has been found to serve an important role in cell proliferation and metastasis by acting through cancer-related mirnas (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)53,54).…”

“…To establish whether p53 gene exerted its activity through micrornas (miRNAs), RT-qPCR was performed to determine the levels of mirnas in mBM-MScs with differential p53 expression, that have previously been reported to serve vital roles in cancer progression, including mir-221, mir-155, mir-1288, mir-4669, mir-3152 and mir-337 ( Fig. 6a) (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). The expression levels of mir-3152 and mir-337 were significantly increased in p53 +/and p53 -/-mBM-MScs compared with p53 +/+ mBM-MScs, whereas the expression levels of mir-221, mir-155, mir-1288 and mir-4669 were significantly decreased in p53 +/and p53 -/-mBM-MScs compared with p53 +/+ mBM-MScs (Fig.…”

The micro RNA hsa-miR-377-3p inhibits tumor growth in malignant melanoma

“…MiR-377-3p, mentioned as a tumor suppressor in many literature studies, negatively regulates glioma cell proliferation and migration 37 and is a prognostic marker in squamous cell carcinoma. 38 Moreover, miR-377-3p is also involved in some stem cell differentiation. 39 The specic functions of miR-377-3p in a great deal of human cancers have been identied; however, limited data are available about its changes and roles in cutaneous malignant melanoma.…”