Find in Library
Search millions of books, articles, and more
Indexed Open Access Databases
Identification of Tumor-Suppressive <i>miR-30e-3p</i> Targets: Involvement of <i>SERPINE1</i> in the Molecular Pathogenesis of Head and Neck Squamous Cell Carcinoma
oleh: Chikashi Minemura, Shunichi Asai, Ayaka Koma, Ikuko Kase-Kato, Nozomi Tanaka, Naoko Kikkawa, Atsushi Kasamatsu, Hidetaka Yokoe, Toyoyuki Hanazawa, Katsuhiro Uzawa, Naohiko Seki
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2022-03-01 |
Deskripsi
Recently, our studies revealed that some passenger strands of microRNAs (miRNAs) were closely involved in cancer pathogenesis. Analysis of miRNA expression signatures showed that the expression of <i>miR-30e-3p</i> (the passenger strand of pre-<i>miR-30e</i>) was significantly downregulated in cancer tissues. In this study, we focused on <i>miR-30e-3p</i> (the passenger strand of pre-<i>miR-30e</i>). We addressed target genes controlled by <i>miR-30e-3p</i> that were closely associated with the molecular pathogenesis of head and neck squamous cell carcinoma (HNSCC). Ectopic expression assays demonstrated that the expression of <i>miR-30e-3p</i> attenuated cancer cell malignant phenotypes (e.g., cell proliferation, migration, and invasive abilities). Our analysis of <i>miR-30e-3p</i> targets revealed that 11 genes (<i>ADA</i>, <i>CPNE8</i>, <i>C14orf126</i>, <i>ERGIC2</i>, <i>HMGA2</i>, <i>PLS3</i>, <i>PSMD10</i>, <i>RALB</i>, <i>SERPINE1</i>, <i>SFXN1,</i> and <i>TMEM87B</i>) were expressed at high levels in HNSCC patients. Moreover, they significantly predicted the short survival of HNSCC patients based on 5-year overall survival rates (<i>p</i> < 0.05) in The Cancer Genome Atlas (TCGA). Among these targets, <i>SERPINE1</i> was found to be an independent prognostic factor for patient survival (multivariate Cox regression; hazard ratio = 1.6078, <i>p</i> < 0.05). Aberrant expression of <i>SERPINE1</i> was observed in HNSCC clinical samples by immunohistochemical analysis. Functional assays by targeting <i>SERPINE1</i> expression revealed that the malignant phenotypes (e.g., proliferation, migration, and invasion abilities) of HNSCC cells were suppressed by the silencing of <i>SERPINE1</i> expression. Our miRNA-based approach will accelerate our understanding of the molecular pathogenesis of HNSCC.