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Head and neck squamous cell carcinoma (HnScc) is highly prevalent worldwide, and the outcome of HnScc is still difficult to predict due to the lack of appropriate prognostic markers. in the present study, a prognostic model based on a mirna panel was established to better predict the survival of HnScc patients. mirna expression data and clinical information regarding HnScc patients were acquired from The cancer Genome atlas (TcGa) database. accompanying clinical data was obtained from the university of california, Santa cruz (ucSc) Xena browser. using this data, 140 differentially expressed miRNAs (DEMs) were identified between HnScc tissue samples (n=525) and adjacent normal tissue samples (n=44). The present prognostic model included seven mirnas (i.e. hsa-mir-499a, hsa-mir-548k, hsa-mir-3619, hsa-mir-99a, hsa-mir-137, hsa-mir-3170, and hsa-mir-654), which were identified using least absolute shrinkage and selection operator (laSSo) and cox regression analyses. The independence of the predictive power of this model was validated by further analyses using clinical information. The outstanding performance of the seven-mirna prognostic model was confirmed by time-dependent receiver operating characteristic curve (roc) analysis. These results indicated that combining the mirna panel with pathological characteristics may provide a more accurate prognosis for HnScc. Functional identification of the target genes of the focal mirnas using Gene ontology (Go) and Kyoto encyclopedia of Genes and Genomes (KeGG) pathway enrichment analyses were also performed. The present study demonstrated that the novel mirna panel reported here may be useful in making different prognoses and may improve the clinical management of patients with HnScc.

Emerging evidence suggests that the cancer stem cells (CSCs) are key culprits of cancer metastasis and drug resistance. Understanding mechanisms regulating the critical oncogenic pathways and CSCs function could reveal new diagnostic and therapeutic strategies. We now report that miR-22, a miRNA critical for hair follicle stem/progenitor cell differentiation, promotes tumor initiation, progression, and metastasis by maintaining Wnt/β-catenin signaling and CSCs function. Mechanistically, we find that miR-22 facilitates β-catenin stabilization through directly repressing citrullinase PAD2. Moreover, miR-22 also relieves DKK1-mediated repression of Wnt/β-catenin signaling by targeting a FosB-DDK1 transcriptional axis. miR-22 knockout mice showed attenuated Wnt/β-catenin activity and Lgr5+ CSCs penetrance, resulting in reduced occurrence, progression, and metastasis of chemically induced cutaneous squamous cell carcinoma (cSCC). Clinically, miR-22 is abundantly expressed in human cSCC. Its expression is even further elevated in the CSCs proportion, which negatively correlates with PAD2 and FosB expression. Inhibition of miR-22 markedly suppressed cSCC progression and increased chemotherapy sensitivity in vitro and in xenograft mice. Together, our results revealed a novel miR-22-WNT-CSCs regulatory mechanism in cSCC and highlight the important clinical application prospects of miR-22, a common target molecule for Wnt/β-catenin signaling and CSCs, for patient stratification and therapeutic intervention.