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MicroRNAs (miRNAs) have been regarded as important regulators in different pathological processes of cells. Abnormal expression of miRNAs is frequently associated with cell proliferation, metastasis and apoptosis in various cancers. This study aimed to explore the effect of miR-146-5p on cell growth, metastasis and its mechanism in lung cancer cells. The expressions of miR-146-5p and claudin-12 in A549 and WI-38 cells were altered by transient transfection. Cisplatin was used to develop cells for regulation of cisplatin sensitivity. Cell viability, migration, invasion, and apoptosis were analyzed by CCK-8, Transwell and flow cytometry assays. The protein expressions of Wnt/ β -catenin and PI3K/AKT/MAPK pathway-related factors were detected. miR-146-5p suppression inhibited cell viability, migration and invasion but promoted apoptosis in A549 cells. Moreover, overexpression of miR-146-5p reduced the sensitivity of A549 cells and WI-38 cells to cisplatin. In addition, claudin-12 was a direct target of miR-146-5p and was negatively regulated by miR-146-5p. Claudin-12 silence significantly reversed miR-146-5p suppression-mediated anti-tumor effects in A549 cells. Furthermore, miR-146-5p overexpression activated Wnt/ β -catenin and PI3K/AKT/MAPK signal pathways via down-regulation of claudin-12. The results indicated that miR-146-5p promoted cell viability, migration and invasion, inhibited apoptosis and activated Wnt/ β -catenin and PI3K/AKT/MAPK signal pathways by regulating claudin-12 expression in lung cancer cells. [ABSTRACT FROM AUTHOR]

Protocadherin8 (PCDH8), an integral membrane protein, was reported to be a tumor suppressor involved in tumorigenesis in cancers. We aimed to investigate the expression of PCDH8 and its clinicopathological significance in hypopharyngeal carcinoma. We also examined the possible inactivation mechanism of PCDH8. A total of 80 pairs of hypopharyngeal carcinoma tumor tissues and non-tumor tissues were investigated to examine the immunohistochemical expression of PCDH8. Prognostic value and clinicopathological significance of PCDH8 expression were examined by Kaplan-Meier and log-rank test and Cox’s ones. Ten pairs of tumor tissues and non-tumor tissues were analyzed by RT-PCR and 4 pairs by Western blot respectively. Promoter methylation of PCDH8 was observed in 14 pairs of tumor tissues and non-tumor tissues by methylation-specific PCR (MSP). The expression of PCDH8 in tumor tissues was depressed immunohistochemically when compared with non-tumor tissues and was significantly lower in the advanced pathological stage. Meanwhile, the expression of PCDH8 served as an independent prognostic risk factor for overall survival of hypopharyngeal carcinoma. The mRNA and protein levels of PCDH8 in tumor tissues was also down-regulated than in non-tumor tissues. Moreover, aberrant promoter methylation of PCDH8 occurred frequently in tumor tissues, rather than in non-tumor tissues. For the first time, our study demonstrates the tumor-suppressive function of PCDH8 and its epigenetic inactivation by promoter methylation in hypopharyngeal carcinoma. It suggests that PCDH8 may serve as a useful prognostic biomarker and a potential therapeutic target for hypopharyngeal carcinoma patients. [ABSTRACT FROM AUTHOR]