Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and its incidence continues to rise.,Although CSCC usually display a benign clinical behavior, it can be both locally invasive and metastatic.,The signaling pathways involved in CSCC development have given rise to targetable molecules in recent decades.,In addition, the high mutational burden and increased risk of CSCC in patients under immunosuppression were part of the rationale for developing the immunotherapy for CSCC that has changed the therapeutic landscape.,This review focuses on the molecular basis of CSCC and the current biology-based approaches of targeted therapies and immune checkpoint inhibitors.,Another purpose of this review is to explore the landscape of drugs that may induce or contribute to the development of CSCC.,Beginning with the pathogenetic basis of these drug-induced CSCCs, we move on to consider potential therapeutic opportunities for overcoming this adverse effect.
Previous studies have revealed that dysregulation of long non-coding RNAs (lncRNAs) can facilitate carcinogenesis.,This study aims to investigate the biological role of a certain lncRNA in cutaneous squamous cell carcinoma (CSCC).,According to the data of TCGA database, high expression of long intergenic non-protein coding RNA 1048 (LINC01048) is an unfavorable prognostic factor for patients with CSCC.,Therefore, we further detected the expression pattern of LINC01048 in CSCC tissues.,Obviously, LINC01048 was expressed higher in the CSCC tissues and recurrence tissues compared with that in adjacent normal tissues and non-recurrence tissues.,Furthermore, Kaplan-Meier analysis revealed the negative correlation between LINC01048 expression and the overall survival and disease-free survival of CSCC patients.,Subsequently, functional assays were conducted to prove the inhibitory effect of silenced LINC01048 on the proliferation and apoptosis of CSCC cells.,Mechanistically, LINC01048 was proved to be transcriptionally activated by USF1.,Pathway analysis and western blot assay showed that knockdown of LINC01048 led to the activation of Hippo pathway.,Moreover, YAP1, a Hippo pathway factor, was positively regulated by LINC01048.,Further mechanism investigation revealed that LINC01048 increased the binding of TAF15 to YAP1 promoter to transcriptionally activate YAP1 in CSCC cells.,Finally, rescue assays demonstrated that YAP1 involved in LINC01048-mediated CSCC cell proliferation and apoptosis.,In conclusion, USF1-induced upregulation of LINC01048 promoted CSCC by interacting with TAF15 to upregulate YAP1.