HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2

Abstract

Homeobox C6 (HOXC6) is a transcription factor that plays a role in the malignant progression of various cancers. However, the roles of HOXC6 and its regulatory mechanism remain unclear. In this study, we used microRNA (miRNA) regulatory networks to identify key regulatory interactions responsible for HOXC6-mediated cancer progression. In microarray profiling of miRNAs, the levels of miRNAs such as hsa-miR-188-5p, hsa-miR-8063, and hsa-miR-8064 were significantly increased in HOXC6-overexpressing cells. Higher positive expression rates of HOXC6 and miR-188-5p were observed in malignant cancer. We also found that HOXC6 significantly upregulated miR-188-5p expression. The underlying function of HOXC6-mediated miR-188-5p expression was predicted through TargetScan and the MiRNA Database. Overexpression of mir-188-5p inhibited the expression of forkhead box N2 (FOXN2), a tumor suppressor gene. Furthermore, in the luciferase assay, miR-188-5p bound to the 3′-UTR of FOXN2 and was mainly responsible for the dysregulation of FOXN2 expression. Silencing FOXN2 induced cell migration, and the effect of FOXN2 silencing was enhanced when the HOXC6/miR-188-5p axis was induced. These results suggest that HOXC6/miR-188-5p may induce malignant progression in cancer by inhibiting the activation of the FOXN2 signaling pathway.

Comprehensive bioinformatics analysis reveals the significance of forkhead box family members in pancreatic adenocarcinoma

“…Contradicting our results, previous studies have shown that FOXN2 may serve as a tumor suppressor in breast cancer [ 10 ], lung cancer [ 11 ], and human oral cancer [ 12 ]. The degradation of FOXN2 promotes tumorigenesis and radioresistance in lung cancer cells [ 11 ], but our results identified FOXN2 as a possible oncogene in PAAD ( Figures 1B , 2B ).…”

Identification and characterization of virus-encoded circular RNAs in host cells

“…S2(f–k). According to the literature, hsa-miR-8063 was found to inhibit pancreatic cancer progression through inducing inhibition on ZFP91 [63], to suppress the epithelial–mesenchymal transition of lung cancer cells by regulating its target gene MAGAT3 [64], and to induce cell migration through inhibition of the tumour suppressor FOXN2 [65]. Hsa-mir-4745–5p was strongly dysregulated in Parkinson’s disease (PD) and can be directly regulated by HNF4a [66], which was identified as a longitudinal PD blood biomarker [67].…”

Transcriptomic and Metabolomic Analysis of Liver Cirrhosis

“…Hsa-miR-188-5p is highly expressed in cancer and can be used as a prognostic indicator in HCC [ 26 , 27 ]. Our results showed that hsa-miR-188-5p expression was remarkably elevated in cirrhosis.…”