• Long Non-Coding RNAs and HPV Associated Cutaneous cancer
  • Niloofar Faraji Lahijani,1,* Tahereh Zeinali,2 Narges Eslami,3
    1. Gastrointestinal and Liver Diseases Research Center, Razi Hospital, Guilan University of Medical Science, Rasht, Iran
    2. Gastrointestinal and Liver Diseases Research Center, Razi Hospital, Guilan University of Medical Science, Rasht, Iran
    3. Gastrointestinal and Liver Diseases Research Center, Razi Hospital, Guilan University of Medical Science, Rasht, Iran


  • Introduction: Cutaneous cancer rates are on the rise, with various types, including melanoma and non-melanoma, becoming more prevalent. This increase stems from a complex mix of inherited traits, gene expression changes, and environmental exposures. Notably, human papillomavirus (HPV) infection has emerged as a significant factor in the development of these skin-based tumors. Non-coding RNAs (lncRNAs) have emerged as critical players in developing and progressing HPV-positive cutaneous cancers.
  • Methods: This comprehensive review explores the intricate relationships between lncRNAs, microRNAs (miRNAs), and HPV oncoproteins in the context of skin cancer pathogenesis.
  • Results: Some lncRNAs are competing endogenous RNAs (ceRNAs), capable of sponging miRNAs and influencing their tumor suppressor functions. This interaction can increase carcinogenesis by preventing miRNAs from silencing their oncogenic targets. LncRNAs are classified into intronic, sense-overlapping, antisense, and long intergenic non-coding RNAs (lincRNAs), each with distinct regulatory functions in cancer progression. The subcellular localization of lncRNAs is crucial to their function. Nuclear lncRNAs primarily modify chromatin to regulate transcription, while cytoplasmic lncRNAs influence mRNA stability and translation, thus modulating protein expression. HPV oncoproteins, particularly E6 and E7, play a significant role in regulating epithelial differentiation by controlling the expression of pro-differentiation (TINCR) and anti-differentiation (DANCR) lncRNAs. Are various lncRNAs implicated in melanoma and non-melanoma cancers, including PVT1, MALAT1, HOTAIR, NEAT1, etc. These lncRNAs interact with multiple signaling pathways, such as TGF-β1, Wnt/β-catenin, Notch, Hippo, Akt/mTOR, SHP2/ERK, and NF-κB, contributing to cancer development through alterations in cell proliferation, death, cycle, migration, angiogenesis, and invasion. PVT1, an oncogenic lncRNA highly expressed in HPV-positive cancers, stabilizes MYC, enhancing the aggressive characteristics of cancer cells. Its upregulation is associated with squamous cell carcinoma (SCC) progression in the skin, suggesting a crucial role in the multistage carcinogenesis process of cutaneous SCC. The review details PVT1's interaction with 4E-binding protein 1 (4EBP1), a tumor suppressor that modulates the mTOR signaling pathway, highlighting the complex regulatory mechanisms in cutaneous SCC. Moreover, lncRNAs play a role in modulating immune responses and radiation sensitivity in HPV-related cancers. LncRNA PRINS alters the expression profiles of genes associated with immune and antiviral responses in HPV-induced head and neck SCC. Lnc-IL17RA-11 targets genes involved in cell replication and proliferation, potentially increasing the sensitivity of HPV-associated head and neck SCC cells to radiation therapy. Furthermore, lncRNAs can function as molecular sponges for HPV-related miRNAs. Several lncRNA/miRNA pairs, such as HOTAIR/miR-214-3p and MALAT1/miR-216b, are highlighted for their cooperative contribution to developing HPV-related cancers. In vivo studies demonstrating the effects of PVT1 knockdown on cutaneous SCC cells are presented, showing significant inhibition of proliferation, migration, and invasion both in vitro and in vivo.
  • Conclusion: These findings underscore the potential of targeting PVT1 as a therapeutic strategy in cutaneous SCC treatment. This comprehensive overview underscores the significance of lncRNAs in the pathogenesis of cutaneous cancers and their potential as diagnostic and prognostic biomarkers, paving the way for novel treatment strategies in managing HPV-positive skin malignancies.
  • Keywords: Human papillomavirus; Cutaneous cancer; Long non-coding RNA