Identification of Antitumor miR-30e-5p Controlled Genes; Diagnostic and Prognostic Biomarkers for Head and Neck Squamous Cell Carcinoma

作者：Chikashi Minemura, Shunichi Asai, Ayaka Koma, Naoko Kikkawa, Mayuko Kato, Atsushi Kasamatsu, Katsuhiro Uzawa, Toyoyuki Hanazawa, Naohiko Seki · 发表于：Genes · 年份：2022 · DOI：10.3390/genes13071225 · 被引用次数：6 · 研究领域：Cancer-related molecular mechanisms research、MicroRNA in disease regulation、RNA modifications and cancer

Analysis of microRNA (miRNA) expression signatures in head and neck squamous cell carcinoma (HNSCC) has revealed that the miR-30 family is frequently downregulated in cancer tissues. The Cancer Genome Atlas (TCGA) database confirms that all members of the miR-30 family (except miR-30c-5p) are downregulated in HNSCC tissues. Moreover, low expression of miR-30e-5p and miR-30c-1-3p significantly predicts shorter survival of HNSCC patients (p = 0.0081 and p = 0.0224, respectively). In this study, we focused on miR-30e-5p to investigate its tumor-suppressive roles and its control of oncogenic genes in HNSCC cells. Transient expression of miR-30e-5p significantly attenuated cancer cell migration and invasive abilities in HNSCC cells. Nine genes (DDIT4, FOXD1, FXR1, FZD2, HMGB3, MINPP1, PAWR, PFN2, and RTN4R) were identified as putative targets of miR-30e-5p control. Their expression levels significantly predicted shorter survival of HNSCC patients (p < 0.05). Among those targets, FOXD1 expression appeared to be an independent factor predicting patient survival according to multivariate Cox regression analysis (p = 0.049). Knockdown assays using siRNAs corresponding to FOXD1 showed that malignant phenotypes (e.g., cell proliferation, migration, and invasive abilities) of HNSCC cells were significantly suppressed. Overexpression of FOXD1 was confirmed by immunostaining of HNSCC clinical specimens. Our miRNA-based approach is an effective strategy for the identification of prognostic ...