CDKN1B 109VG and CDKN2A (540CG & 580CT) polymorphisms and susceptibility to colorectal cancer: A case-control study of the Iranian population
GENE REPORTS
Authors: Gohari, Nazanin; Saadat, Iraj
Abstract
Background: One of the most important factors leading to tumorigenesis is abnormality in the cells proliferation, because of the irregularity in cell cycle progression. CDKN2A (p16) and CDKN1B (p27) are tumor suppressors and regulators of cell cycle at G1 and G1-S transition. Any disorders in activity or expression of these two tumor suppressors can cause cancer. Aims: In this study, we appraised the relationship between 3 polymorphisms: p27 109VG (rs2066827) in exon1 and p16 [540CG (rs11515), 580CT (rs3088440)] in 3'UTR with the risk of colorectal cancer susceptibility in Iranian population. Subjects and methods: This case-control study was carried out on 214 cases with CRC and 233 control subjects. For p27 109VG and p16 (540CG, 580CT) genotyping, PCR-RFLP technique was used. Results: Logistic regression analysis revealed that G allele of p16 540CG significantly decreased the risk of CRC (OR = 0.63, CI = 0.42- 0.95, P = 0.031), but subjects with TT genotype of 580CT are more likely to develop CRC (OR = 4.63, CI = 1.28-16.71, P = 0.019). There were no significant relationships with p27 109VG and haplotype of p16 (540CG, 580CT) with CRC risk in Iranian population. However, coincidence in VG genotype of p27 109VG and CC genotype of p16 540CG has significantly increased the susceptibility to colorectal cancer (OR = 2.02, CI = 1.02-3.98, P = 0.042). Conclusion: This study indicates that the p16 [540CG (rs11515), 580CT (rs3088440)] polymorphisms are associated with the risk of CRC in Iranian population.
Upregulated Circular RNA hsa_circ_0008433 Regulates Pathogenesis in Endometriosis Via miRNA
REPRODUCTIVE SCIENCES
Authors: Jiang, Nan; Pan, Wenwei; Li, Jinhui; Cao, Tiefeng; Shen, Huimin
Abstract
circRNAs (circular RNAs) play important roles in the development of endometriosis. This study aimed to explore the functions of circRNAs on endometriosis. Two ectopic, two paired eutopic, and two normal endometrial tissue samples were collected for RNA-seq to obtain circRNA profiles and construct a circRNA-miRNA-mRNA network. The validation of 9 circRNAs in 15 patients was assessed by qRT-PCR. We selected hsa_circ_0008433 as the potential biomarker, followed by examining cell proliferation, colony formation, migration, angiopoiesis, cell cycle, and apoptosis. Furthermore, the expression of apoptosis-related proteins was detected using immunofluorescence (IF) and Western blotting. Bioinformatic analysis was used to select the potential target miRNA and genes of hsa_circ_0008433. A total of 209 upregulated and 117 downregulated differentially expressed circRNAs were identified from the eutopic and ectopic endometrial tissue samples. Eight circRNA levels were significantly increased in ectopic endometrial tissue sample compared with eutopic endometrial tissue. The hsa_circ_0008433 knockdown inhibited endometrial stromal cell proliferation, migration, colony formation, and angiopoiesis; promoted cell apoptosis; and downregulated Ki67 and PCNA expression levels. Moreover, the hsa_circ_0008433 knockdown increased Bax and E-CAD expression and decreased Bcl2, CDKN1B, and CyclinD1 levels. Ten potential target miRNAs of hsa_circ_0008433 were selected, and six of them occur significantly aberrant in hsa_circ_0008433-expressing cells. Increased hsa_circ_0008433 levels regulate epithelial mesenchymal transition (EMT) in endometriosis through the circRNA-miRNA-mRNA axis.