Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide, which is associated with a poor prognosis. The present study aimed to investigate the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in OSCC and its regulatory effect on AKT1. Firstly, CIP2A and AKT1 expression in OSCC cells was detected by western blotting. After silencing CIP2A, cell viability and cell proliferation were assessed using the Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine staining. Cell apoptosis was evaluated by TUNEL staining and the expression of apoptosis-related proteins was assessed using western blotting. Wound healing, Transwell and tube formation assays were performed to evaluate CAL-27 cell migration, invasion and human umbilical vein endothelial cell (HUVEC) tube formation. The interaction between CIP2A and AKT1 was identified by co-immunoprecipitation (co-IP). In addition, AKT1 was overexpressed in CIP2A-silenced CAL-27 cells to perform rescue experiments to analyze the malignant biological functions of CAL-27 cells. Finally, the expression of proteins in the glycogen synthase kinase (GSK)-3β/β-catenin pathway was determined by western blot analysis. Markedly elevated CIP2A and AKT1 expression was observed in OSCC cells. CIP2A knockdown inhibited the viability, proliferation, migration and invasion, and promoted the apoptosis of CAL-27 cells. Concurrently, CIP2A loss-of-function attenuated tube formation. Results of Co-IP confirmed there was an interaction between CIP2A and AKT1. Rescue experiments suggested that AKT1 overexpression alleviated the inhibitory effects of CIP2A knockdown on the viability, proliferation, migration and invasion of CAL-27 cells, as well as tube formation in HUVECs . Additionally, CIP2A silencing significantly downregulated phosphorylated-GSK-3β and β-catenin expression, which was reversed by AKT1 overexpression. In conclusion, CIP2A could interact with AKT1 to promote the malignant biological behaviors of OSCC cells by upregulating the GSK-3β/β-catenin pathway. These findings may provide a targeted therapy for OSCC treatment.

The long non-coding RNA X inactive-specific transcript (XIST) has been implicated in certain human cancers, including osteosarcoma (OS), but the molecular mechanism of XIST underlying OS progression remains to be fully uncovered. In the present study, reverse transcription-quantitative polymerase chain reaction data demonstrated that XIST was significantly upregulated in OS tissues and cell lines (Saos-2, U2OS, HOS and MG63) compared with adjacent non-tumour tissues and normal human osteoblast cell line HFOB1.19. Bioinformatics analysis and luciferase reporter gene assay data demonstrated that XIST could directly target microRNA (miR)-137 and negatively regulate the expression of miR-137 in Saos-2 and U2OS cells. Furthermore, miR-137 was markedly downregulated in OS tissues and cell lines. An inverse association between XIST and miR-137 expression was observed in OS tissues. Knockdown of XIST caused a significant reduction in cell proliferation and invasion and suppressed matrix metalloproteinase (MMP2) and MMP9 protein levels in Saos-2 and U2OS cells. Furthermore, inhibition of miR-137 expression abolished the effects of XIST downregulation on the proliferation and invasion of OS cells. In summary, the present study suggests that XIST promotes OS cell proliferation and invasion by inhibition of miR-137 expression. Thus, XIST may be a potential therapeutic target for the treatment of OS.

Malignant melanoma (MM) is the most aggressive form of skin cancer originating from melanocytes with increased proliferative and metastatic ability. Previous studies have revealed that microRNA-338-3p (miR-338-3p) functions as a tumor suppressor in several types of cancer, including cervical cancer, renal cell carcinoma and thyroid cancer. However, the function and mechanism underlying the action of miR-383-3p in MM remain unclear. In the study, aberrant downregulation of miR-338-3p was observed in 60 pairs of MM and adjacent non-tumor tissue using quantitative polymerase chain reaction assay. Decreased miR-383-3p expression was associated with advanced clinical stage (P<0.05) and lymph node metastasis (P<0.001). The overexpression of miR-338-3p in A375 and G361 cells suppressed cell proliferation and migration using MTT, colony formation, wound healing and transwell assays. Mechanistically, MACC1 was identified as a direct target for miR-338-3p using bioinformatics prediction and dual-luciferase assays. Furthermore, MACC1 expression was significantly increased and inversely correlated with the levels of miR-338-3p in MM tissues. More importantly, restoration of MACC1 resulted in reversed the inhibitory effects of miR-338-3p overexpression on MM cells by altering the expression levels of PCNA and epithelial-mesenchymal transition (EMT)-associated proteins. These results suggest that miR-338-3p functions as a novel tumor suppressor, at least in part, via targeting MACC1 and suggest that miR-338-3p may serve as a potential target for treatment of MM patients.