Blood Serum From Head and Neck Squamous Cell Carcinoma Patients Induces Altered MicroRNA and Target Gene Expression Profile in Treated Cells

Abstract

The head and neck squamous cell carcinoma (HNSCC) represents one of the most common cancers in humans. Close to 600,000 new diagnoses are made every year worldwide and over half of diagnosed patients will not survive. In view of this low survival rate, the development of novel cell-based assays for HNSCC will allow more mechanistic approaches for specific diagnostics for each individual patient. The cell-based assays will provide more informative data predicting cellular processes in treated patient, which in effect would improve patient follow up. More importantly, it will increase the specificity and effectiveness of therapeutic approaches. In this study, we investigated the role of serum from HNSCC patients on the regulation of microRNA (miRNA) expression in exposed cells in vitro. Next-generation sequencing of miRNA revealed that serum from HNSCC patients induced a different miRNA expression profile than the serum from healthy individuals. Out of 377 miRNA detected, we found that 16 miRNAs were differentially expressed when comparing cells exposed to serum from HNSCC or healthy individuals. The analysis of gene ontologies and pathway analysis revealed that these miRNA target genes were involved in biological cancer-related processes, including cell cycle and apoptosis. The real-time PCR analysis revealed that serum from HNSCC patients downregulate the expression level of five genes involved in carcinogenesis and two of these genes—P53 and SLC2A1—are direct targets of detected miRNAs. These novel findings provide new insight into how cancer-associated factors in circulation regulate the expression of genes and regulatory elements in distal cells in favor of tumorigenesis. This has the potential for new therapeutic approaches and more specific diagnostics with tumor-specific cell lines or single-cell in vitro assays for personalized treatment and early detection of primary tumors or metastasis.

Long non‐coding RNA MIF‐AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4

“…The downregulated SCD1 has been found to significantly reduce the formation and metastasis of melanoma in vitro and in vivo . However, the elevated expression level of miR‐212‐5p has been reported in head and neck squamous cell carcinomas and in melanoma . Herein, we showed the tumor‐suppressing role of miR‐212‐5p in gastric cancer in that miR‐212‐5p overexpression obviously attenuated the proliferation ability and increased the apoptotic rate of gastric cancer cells in vitro.…”

miR‐451a inhibits cancer growth, epithelial‐mesenchymal transition and induces apoptosis in papillary thyroid cancer by targeting PSMB8

“…Furthermore, free miRNAs could be detected in human body fluids like serum. The expression profile of cancer patients’ serum miRNAs differs significantly from healthy people's expression profile . This makes serum miRNAs promising candidates of novel biomarkers for cancer detection .…”

“…The expression profile of cancer patients' serum miRNAs differs significantly from healthy people's expression profile. [13][14][15] This makes serum miRNAs promising candidates of novel biomarkers for cancer detection. 16 Several studies have reported the close correlation between miR-451a and PTC progression.…”

Bioinformatics analysis of the expression and role of microRNA-221-3p in the head and neck squamous cell carcinoma

“…Head and neck squamous cell carcinoma (HNSCC)encompassing the oral squamous cell carcinoma, oropharyngeal squamous cell carcinoma, hypopharyngeal squamous cell carcinoma and laryngeal squamous cell carcinoma is the sixth most common cancer worldwide, accounting for approximately 1-2% of all cancer deaths, with about 600,000 detection of new cases each year globally [1,2,3].The treatment of patients at the early stage is relatively successful, but the overall survival rate of recurrent or metastatic HNSCC remains low and has barely seen any improvements in their survival for decades [4,5]. Although the past three decades have seen several improvements in the diagnostic tools and treatment regimens, the overall survival rate for the advanced (stage Ⅲ-Ⅳ) head and neck squamous cell carcinoma (HNSCC) is only 65% [6,7].…”

“…Studies have shown that specific miRNA profiles can be identified between tumor tissue and adjacent healthy tissue in the HNSCC patients [2,23]. For instance, studies have reported the link between miR-211 and vascular invasion during the incidence of HNSCC [14,15,24,25,26].…”