Knockdown of TMEM132A restrains the malignant phenotype of gastric cancer cells via inhibiting Wnt signaling.

Transmembrane protein 132 A (TMEM132A) has been recently reported to be a novel regulator of the Wnt signaling pathway, which is a cancer-associated cascade. However, the role of TMEM132A in cancer is not well characterized. Here, we used bioinformatics analysis to analyze the differential expression of TMEM132A in gastric cancer (GC) tissues and determine its diagnostic and prognostic value. Results showed that TMEM132A expression was upregulated in GC tissues. TMEM132A was also found to have diagnostic and prognostic roles in patient with GC. Furthermore, as evaluated by in vitro assays, knockdown of TMEM132A restrained cell proliferation, migration, and invasion of GC cells, while overexpression of TMEM132A exerted opposite effects. However, the effects of TMEM132A silencing and overexpression on GC cells were reversed by treatment with LiCl and ICG-001 (the Wnt signaling activator and inhibitor), respectively. In addition, in vivo assays showed that knockdown of TMEM132A suppressed GC tumorigenesis. Hence, our results provide new insights into the oncogenic role of TMEM132A in regulating GC cell proliferation, migration, and invasion, as well as its prognostic and therapeutic roles in patients with GC. These data highlight the diagnostic, prognostic, and therapeutic potential of TMEM132A in GC.

PAK4, a target of miR-9-5p, promotes cell proliferation and inhibits apoptosis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. P21-activated kinase 4 (PAK4) and miR-9-5p have emerged as attractive therapeutic targets in several tumor types, but in CRC, the regulation of their biological function and their target association remain unclear. METHODS: The expression of PAK4 in CRC tissues was determined using quantitative real-time PCR and immunohistochemistry analyses. The targeted regulation between miR-9-5p and PAK4 was predicted and confirmed with bioinformatics analysis and the dual-luciferase reporter assay. Functional experiments, including the MTT assay and flow cytometry, were performed to investigate the impact of PAK4 knockdown and miR-9-5p overexpression on cell proliferation and apoptosis in CRC cells. RESULTS: We found that the expression of PAK4 was upregulated in CRC tissues. PAK4 knockdown significantly suppressed cell proliferation and promoted apoptosis in cells of the CRC cell lines HCT116 and SW1116. We also found that miR-9-5p directly targeted the 3'-UTR of PAK4 mRNA and negatively regulated its expression. The degree of downregulation of miR-9-5p inversely correlated with PAK4 expression. Intriguingly, enforced expression of miR-9-5p suppressed cell proliferation and promoted apoptosis. This could be partially reversed by PAK4 overexpression. CONCLUSION: These results suggest that miR-9-5p targeting of PAK4 could have therapeutic potential for CRC treatment.