MiR-497-5p inhibits cell proliferation and metastasis in hepatocellular carcinoma by targeting insulin-like growth factor 1.

BACKGROUND: MicroRNAs (miRNAs) play an important regulatory role in carcinogenesis and cancer progression. Aberrant expression of miR-497-5p has been reported in various human malignancies. However, the role of miR-497-5p in hepatocellular carcinoma (HCC) remains unclear. RESULTS: In this study, we found that miR-497-5p was downregulated in HCC tissues. The low level of miR-497-5p in HCC tumors was correlated with aggressive clinicopathological characteristics and predicted poor prognosis in HCC patients. The overexpression of miR-497-5p significantly inhibited HCC cell proliferation, colony formation, and metastasis in vitro and vivo. Bioinformatics analysis further identified insulin-like growth factor 1 (IGF1) as a novel target of miR-497-5p in HCC cells. CONCLUSION: Our study suggested that miR-497-5p regulates HCC cell survival, partially through downregulation of IGF1. Therefore, the miR-497-5p/IGF1 axis might serve as a novel therapeutic target in patients with HCC.

Pri-miR-34b/c rs4938723 polymorphism is associated with a decreased risk of gastric cancer.

Previous studies have demonstrated that miR-34 family members are abnormally expressed in gastric cancer. Overexpression of the miR-34 family suppresses gastric carcinogenesis, whereas downregulation of the miR-34 family promotes tumorigenesis. p53 can bind to the promoter region of miR-34b/c, leading to an increase of miR-34b/c expression. Recently, a variant in the promoter region of pri-miR-34b/c (rs4938723) has been discovered, with the function of altering the binding efficiency of transcription factor GATA. The purpose of this study was to examine the role of the miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms in the susceptibility of gastric cancer. We analyzed the distribution of the two polymorphisms in 197 patients with gastric cancer and 289 age-, gender-, ethnicity-, and living area-matched controls using polymerase chain reaction-restriction fragment length polymorphism and DNA direct sequencing. We found that the CT and CT/CC genotypes of the miR-34b/c rs4938723 were associated with a significantly decreased risk of gastric cancer compared with the TT genotype (CT vs. TT: odds ratio [OR]=0.66; 95% confidence interval [95% CI], 0.45-0.97; and CT/CC vs. TT: OR=0.67; 95% CI, 0.47-0.97, respectively). Combined analysis showed that subjects carrying the miR-34b/c rs4938723 CT/CC and TP53 CG/CC genotypes had a 0.62-fold decreased risk to develop gastric cancer compared with subjects carrying the miR-34b/c rs4938723 TT and TP53 CG/CC genotypes (OR=0.62; 95% CI, 0.40-0.96). These findings suggest that the miR-34b/c rs4938723 may individually and jointly have a protective effect on the risk of gastric risk.

A let-7 KRAS rs712 polymorphism increases colorectal cancer risk.

Growing evidence has indicated that polymorphism present in the miRNA binding site of target gene can alter the ability of miRNAs to bind its target gene and modulate the development and progression of cancer. We aimed to investigate the association between let-7 KRAS rs712 polymorphism and the risk of colorectal cancer (CRC). The let-7 KRAS rs712 was analyzed in a case-control study, including 339 CRC patients and 313 age- and sex-matched controls; the relationship between the polymorphism and the clinicopathological features of CRC was also examined. Individuals carrying the let-7 KRAS rs712 TT genotype and T allele had an increased risk of developing CRC (TT vs. GG, adjusted OR = 2.18; 95% CI, 1.00-4.77; T vs. G, adjusted OR = 1.50; 95% CI, 1.15-1.96). Stratified analyses revealed that CRC patients with the let-7 KRAS rs712 TT genotype were more likely to have clinical stage III or IV disease (OR = 3.29, 95% CI, 1.32-8.20) and distant metastasis (OR = 4.70, 95% CI, 1.81-12.25). These findings provide evidence that the let-7 KRAS rs712 polymorphism may play crucial roles in the etiology of CRC.

Vitamin D receptor BsmI polymorphism and osteoporosis risk: a meta-analysis from 26 studies.

OBJECTIVE: Growing evidence has shown that vitamin D deficiency can cause lower bone mineral density (BMD) and an increased risk of osteoporosis. Vitamin D receptor (VDR) BsmI polymorphism (rs1544410) can affect BMD variation and circulating osteocalcin levels. To date, a wide range of epidemiological studies have been carried out to evaluate the association between VDR BsmI polymorphism and susceptibility to osteoporosis. Conflicting results, however, were obtained. The aim of this study was to evaluate the effect of VDR BsmI polymorphism on osteoporosis risk using a meta-analysis. METHODS: Twenty-six publications were identified by searching PubMed and Embase databases. The association between VDR BsmI polymorphism and osteoporosis was estimated by calculating pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS: The bb genotype was associated with a significantly decreased risk of osteoporosis in overall comparison (bb vs. BB: OR=0.61, 95% CI, 0.40-0.92; bb vs. BB/Bb: OR=0.70, 95% CI, 0.52-0.95, respectively). Subgroup analyses showed that the bb genotype had a decreased risk of developing osteoporosis in postmenopausal women (bb vs. BB/Bb: OR=0.68, 95% CI, 0.46-0.98) and Africans (Bb/bb vs. BB: OR=0.18, 95% CI, 0.09-0.37). CONCLUSION: The VDR BsmI polymorphism may have a protective role against the development of osteoporosis.