Expression and molecular regulation of non-coding RNAs in HPV-positive head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide. Accumulating evidence suggests that persistent HPV infection is closely related to a subset of HNSCC types, and the incidence of human papillomavirus (HPV)-positive HNSCC has been annually increasing in recent decades. Although the carcinogenesis of HPV-positive HNSCC has not been completely elucidated, it has been well confirmed that E6 and E7, the main viral oncoproteins are responsible for the maintenance of malignant transformation, promotion of cell proliferation, and increase in tumor invasion. Moreover, compared with HPV-negative HNSCC, HPV-positive HNSCC shows some special clinical-pathological features, which are possibly related to HPV infection and their specific regulatory mechanisms. Non-coding RNA (ncRNA) is a class of RNA lacking the protein-coding function and playing a critical regulatory role via multiple complex molecular mechanisms. NcRNA is an important regulatory pattern of epigenetic modification, which can exert significant effects on HPV-induced tumorigenesis and progression by deregulating downstream genes. However, the knowledge of ncRNAs is still limited, hence, a better understanding of ncRNAs could provide some insights for exploring the carcinogenesis mechanism and identifying valuable biomarkers in HPV-positive HNSCC. Therefore, in this review, we mainly focused on the expression profile of ncRNAs (including lncRNA, miRNA, and circRNA) and explored their regulatory role in HPV-positive HNSCC, aiming to clarify the regulatory mechanism of ncRNAs and identify valuable biomarkers for HPV-positive HNSCC.

Potential Transcript-Based Biomarkers Predicting Clinical Outcomes of HPV-Positive Head and Neck Squamous Cell Carcinoma Patients

“…It is known that E6 binds and degrades p53, promoting the accumulation of mutations and the inhibition of apoptosis, while E7 promotes the continuity of the cell cycle, through the binding and degradation of pRb [29]. Furthermore, HPV oncoproteins have been found to alter the expression profiles of transcripts, including messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), in HNSCC-derived cell lines and HNSCC tumors, which are associated with the promotion of cancerous cellular processes [36][37][38]. The effects induced by viral oncoproteins together with alterations in the cellular genome can lead to cellular transformation towards malignancy, allowing the acquisition of hallmarks of cancer [29].…”

Emerging paradigms: unmasking the role of oxidative stress in HPV-induced carcinogenesis

“…Epigenetic modifications are closely intertwined with gene expression, as they encompass changes to gene function that occur independently in alterations in the DNA sequence [ 117 ]. These modifications could regulate the activation or deactivation of genes [ 118 ]. The diverse range of mechanisms involved in epigenetic changes encompass DNA methylation, histone alterations, and post-transcriptional modifications facilitated by non-coding RNAs such as miRNA [ 119 ].…”