Slug Inhibits Proliferation of Cervical Cancer Cells Through Down-regulating CDH3/β-catenin/C-myc Expression / 肿瘤防治研究

Objective To investigate the related mechanism of Slug inhibiting the proliferation of cervical cancer cell through CDH3/β-catenin/C-myc. Methods SiHa cells with stable Slug expression were screened. The expression of CDH3 in Slug-overexpressed SiHa cell was detected by RNA-sequence, Real-time PCR, Western blot and immunocytochemistry. The expression of CDH3 in SiHa and HeLa cells were detected by Western blot and immunocytochemistry. The protein level of CDH3 was up-regulated in HeLa cells or rescued in SiHa-Slug cells by transient transfection of CDH3 expression vector. The protein levels of β-catenin and C-myc were detected by Western blot, the cell growth was detected by cell counting and CCK-8 assays. Luciferase reporter assay and chromatin immunoprecipitation assay (ChIP) were performed to detect the effect of Slug on regulating the promoter region of CDH3. Results SiHa cell line with stable Slug expression was successfully constructed. Slug overexpression inhibited CDH3 expression in SiHa cells. CDH3 promoted cell proliferation and up-regulated the protein level of β-catenin and C-myc in HeLa and SiHa-Slug cells. Slug could recognize and bind to the E-boxes in the CDH3 promoter region and inhibited the transcription of CDH3 in SiHa cells. Conclusion Slug could inhibit the expression of β-catenin and C-myc by inhibiting CDH3 transcription in SiHa cells, and then attenuate the growth of SiHa cells.

Mutation analysis of causative genes in a case of congenital hypotrichosis / 中华皮肤科杂志

Objective To identify the genetic cause of a case of congenital hypotrichosis by a nextgeneration sequencing technology.Methods A 9-year and 3-month-old girl presented with few villous hairs at birth,which grew slowly.Skin examination showed sparse,thin,soft,woolly and light-yellow hairs,small amount of hairs on the top of the head and a less amount of hairs around the head,hairline recession and broadened forehead.No abnormality was found by ophthalmic examination.No similar aberrant phenotype was observed in the patient's parents or her younger sister.Her parents were non-consanguineous marriage.Peripheral venous blood samples were obtained from the patient,her mother and younger sister.Genomic DNA was extracted and then analyzed by a next-generation sequencing technology.The suspected pathogenic mutations were validated by Sanger sequencing and subjected to bioinformatics analysis.Results Two mutations were identified in the CDH3 gene in the patient,including a c.1057G ＞ T (p.D353Y) heterozygous mutation in exon 5 and a c.1767delC (p.I589Ifs) heterozygous mutation in exon 10.They were both novel mutations,and their pathogenicity was predicted by softwares.Sanger sequencing indicated that the c.1057G ＞ T (p.D353Y) heterozygous mutation was inherited from the patient's mother,and gene transfer analysis revealed that the c.1767delC (p.I589Ifs) heterozygous mutation was inherited from the patient's father.Conclusion The c.1057G ＞ T (p.D353Y) and c.1767delC (p.I589Ifs)heterozygous mutations may cause hypotrichosis and juvenile macular dystrophy in the patient,so careful observation and comprehensive ophthalmic examination should be performed on time for early diagnosis and treatment of eye symptoms.

CDH3/P-Cadherin regulates migration of HuCCT1 cholangiocarcinoma cells / 대한해부학회지

Intrahepatic cholangiocarcinoma is the second most common subtype of primary hepatobilliary cancer. Despite advances in surgical and medical therapy, its survival rate remains poor. Compared to hepatocellular carcinoma (HCC), the most common liver malignancy, the underlying mechanisms of cholangiocarcinoma carcinogenesis are poorly characterized. P-cadherin (CDH3) is a cadherin super family member. Although CDH3 is frequently over-expressed in cholangiocarcinoma tissues, its roles have never been characterized. To determine the roles of CDH3 in cholangiocarcinoma, we investigated CDH3 function in HuCCT1 cells using specific siRNA. Transfection with CDH3 siRNA did not affect proliferation of HuCCT1 cells. However, cell migration and invasion were significantly reduced when CDH3 was down-regulated. In addition, expressions of several biomarkers for epithelial-mesenchymal transition (EMT) were not changed by CDH3 down-regulation. These results suggest that CDH3 regulates cell migration independent of EMT in cholangiocarcinoma cells.