Association between the rs3733846 in the flanking region of miR-143/145 and risk of cervical squamous cell carcinoma.

Aim: To investigate the effect of rs3733846 in the flanking region of miR-143/145 on susceptibility to cervical squamous cell carcinoma (CSCC). Materials & methods: We collected venous blood samples from 242 CSCC patients and 250 healthy controls. The rs3733846 polymorphism was genotyped by SnaPshot and Sanger sequencing. The expression of miR-143/145 in CSCC tissues was detected by quantitative real-time PCR. Results: The rs3733846 AG genotype was associated with a decreased risk of CSCC in genetic model (AGvs.AA: adjusted odds ratio [OR]: 0.44; 95% CI: 0.30-0.66; p < 0.001). Patients with the rs3733846 AG/GG genotypes had a reduced risk of developing poorly differential status (OR: 0.57; 95% CI: 0.33-0.98; p < 0.04) and lymph node metastasis (OR: 0.49; 95% CI: 0.26-0.92; p < 0.03). Conclusion: The rs3733846 in the flanking region of miR-143/145 was related to the susceptibility of CSCC.

ERK Activation-Mediated Autophagy Induction Resists Licochalcone A-Induced Anticancer Activities in Lung Cancer Cells in vitro.

INTRODUCTION: The incidence and mortality rates of lung cancer rank top in the different types of cancers in China. Licochalcone A (LA) is a flavonoid extracted from the roots of licorice with antitumor effects in various cancers in vitro and in vivo. However, the role of LA in non-small cell lung cancer (NSCLC) remains largely unclear. METHODS: The cell viability was measured by MTT assay, Edu staining and colony formation assay. Apoptosis was investigated using Annexin V/PI double-stained assays with flow cytometry. Real-time quantitative RT-PCR was carried out to investigate the expression of mRNA of related proteins. Western blotting was used to investigate the expression of related proteins. RESULTS: The results show that LA inhibits the proliferation of NSCLC cells in a dose-dependent manner and induces apoptotic cell death. Moreover, LA significantly suppresses the expression of c-IAP1, c-IAP2, XIAP, Survivin, c-FLIPL and RIP1 without influencing the level of mRNA. Cycloheximide chase assay demonstrates that LA greatly decreases the stability of Survivin, XIAP and RIP1. Mechanistic studies indicate that LA induces cytoprotective autophagy since block of autophagy with CQ greatly enhances LA-induced anticancer activities. Furthermore, LA rapidly induces ERK and p38 activation in a time-dependent manner in both A549 and H460 cells, but suppresses the activities of c-Jun N-terminal kinase (JNK); suppression of ERK not p38 with inhibitor attenuates LA-induced autophagy, while it remarkably enhances LA-induced cytotoxicity in lung cancer cells and further promotes the degradation of apoptosis-related proteins. DISCUSSION: The results of this study provide novel insights on the role of apoptosis-related proteins and the MAPKs pathway in the anticancer activities of LA.

A genetic variant rs13293512 in the promoter of let-7 is associated with an increased risk of breast cancer in Chinese women.

Growing evidence has demonstrated that single-nucleotide polymorphisms (SNPs) in the promoter of miRNA may influence individuals' susceptibility to human diseases. We examined two SNPs rs10877887 and rs13293512 in the promoters of let-7 family to determine if the two SNPs were related to the occurrence of breast cancer (BC). Genotyping of the two SNPs was performed by PCR and restriction fragment length polymorphism analysis or TaqMan assay in 301 BC patients and 310 age matched controls. We found a higher frequency of rs13293512 CC genotype and rs13293512 C allele amongst BC patients (CC vs TT: adjusted odds ratio (OR) = 1.78; 95% CI: 1.14-2.80; P=0.012; C vs T: adjusted OR = 1.33; 95% CI: 1.06-1.67; P=0.013). Stratification analysis showed that rs13293512 CC genotype was associated with an increased risk of BC in patients with negative estrogen receptor (adjusted OR = 2.39; 95% CI: 1.32-4.30; P=0.004), patients with negative progesterone receptor (adjusted OR = 1.92; 95% CI: 1.11-3.33; P=0.02), patients with T1-2 stage cancer (adjusted OR = 1.77; 95% CI: 1.07-2.93; P=0.03), and patients with N1-3 stage cancer (adjusted OR = 1.89; 95% CI: 1.13-3.17; P=0.015). These findings suggest that rs13293512 in the promoter of let-7a-1/let-7f-1/let-7d cluster may be a possible biomarker for the development of BC in Chinese women.