MiR-455-5p suppresses PDZK1IP1 to promote the motility of oral squamous cell carcinoma and accelerate clinical cancer invasion by regulating partial epithelial-to-mesenchymal transition

Abstract

Background Lymph node and distant metastasis contribute to poor outcomes in patients with oral squamous cell carcinoma (OSCC). The mechanisms regulating cancer migration and invasion play a key role in OSCC. Methods We determined migration and invasion ability of OSCC by wound-healing assay, two-chamber transwell invasion assay and cell mobility tracking and evaluated tumor metastasis in vivo. Western blot (WB), qRT-PCR, RNA-seq, dual-luciferase reporter assays and nuclear/cytoplasmic fractionation were performed to investigate the potential mechanism. Immunohistochimical (IHC) staining determined vimentin and PDZK1IP1 expression in OSCC tissues. Results and conclusion In this study, we determined that miR-455-5p was associated with lymph node metastasis and clinical invasion, leading to poor outcomes in patients with OSCC. MiR-455-5p promoted oral cancer cell migration and invasion and induced epithelial-to-mesenchymal transition (EMT). We also identified a new biomarker, PDZK1IP1 (MAP17), that was targeted by miR-455-5p. PDZK1IP1 knockdown led to migration, metastasis, EMT, and increased transforming growth factor-β signaling in OSCC. In addition, miR-455-5p overexpression and PDZK1IP1 inhibition promoted collective OSCC cell migration. According to data from the Cancer Genome Atlas database and the NCKU-OrCA-40TN data set, miR-455-5p and PDZK1IP1 are positively and negatively correlated, respectively, with partial EMT score. High miR-455-5p expression was associated with high vimentin levels and low MAP17 H-scores. The patients with low MAP17 expression had higher rates of disease recurrence than did patients with high MAP17 expression, especially for patients with clinical invasion risk factors and low MAP17 expression. These results suggest that miR-455-5p suppresses PDZK1IP1 expression and mediates OSCC progression. MiR-455-5p and PDZK1IP1 may therefore serve as key biomarkers and be involved in regulating partial EMT in OSCC cells. PDZK1IP1 expression may also serve as an independent factor that impacts outcomes in patients with clinical risk factors for recurrence.

Possible Role of miR-375-3p in Cervical Lymph Node Metastasis of Oral Squamous Cell Carcinoma

“…Here, we focused on miRNAs associated with the development and progression of human malignancies. Several miRNAs have been reported to function as oncogenes or tumor suppressor genes in OSCC [22][23][24][25][26]. In the present study, we showed that the downregulation of miR-375-3p expression was associated with latent cervical LNM of eOSCC, and the replenishment of miR-375-3p suppressed the growth and migration of human OSCC cells.…”

“…In particular, by regulating gene expression, miRNAs are greatly involved in biological processes such as cell proliferation, migration, infiltration, and apoptosis, which are essential for cancer development and progression [22]. In OSCC, several miRNAs have been reported to be associated with development and progression [22][23][24]. We have also reported several miRNAs that affect tumor growth in OSCC, including miR-361-3p and miR-1289 [25,26].…”

Elk1 enhances inflammatory cell infiltration and exacerbates acute lung injury/acute respiratory distress syndrome by suppressing Fcgr2b transcription

“…Two pathologists, blinded to the study, used a multiheaded microscope to assess protein expression. They evaluated the intensity and distribution to agree on the H-score, calculated as ΣPi (i + 1), where i indicates the intensity of stained cells (0: negative, 1: weak positive, 2: moderate positive, 3: strong positive), and Pi represents the percentage of stained cells (Hsiao et al 2023 ).…”

microRNA-203 inhibits migration and invasion of canine tonsillar squamous cell carcinoma cells by targeting SLUG

“…Many microRNAs (miRNAs and miRs) are associated with EMT in normal and cancer cells (6)(7)(8). However, only a few studies on the association between miRNAs and EMT have been published in veterinary medicine (9)(10)(11).…”