scholarly journals MiRNA-92a Promote Angiogenesis in Colorectal Cancer by Inhibiting the Expression of PTEN

Author(s):  
Xiu Wang ◽  
Yongshen He ◽  
Yu Huang ◽  
Hui Gong ◽  
Lei Wang ◽  
...  

Abstract Background: The microRNA (miRNA) miRNA-92a has been implicated in colorectal cancer (CRC) pathology. Methods: Here, we examined miRNA-92a involvement in CRC-associated angiogenesis, including examining a mechanism by which miRNA-92a may exert such effects. MiRNA-92a expression in 25 clinical CRC samples and in HT29, SW620, SW480 and HCT116 CRC cells was detected with quantitative real-time polymerase chain reaction (qRT-PCR). Blood microvessels were labeled by immunohistochemistry (IHC) with an anti-CD31 antibody. MiR-92a mimic or inhibitor were transfected into HCT116 and SW620 cells to up- and down-regulate miRNA-92a expression, respectively. The effects of altering miRNA-92a expression levels on HUVEC (human umbilical vein endothelial cell) tubule formation and PTEN protein expression were measured. Results: MiRNA-92a was more highly expressed in CRC tissues and cell lines than in matched adjacent tissues (p <0.01) and normal epithelial cells (p <0.05), respectively. Microvessel density (MVD) was elevated in CRC tissues relative to adjacent tissues (p <0.01), and miRNA-92a levels correlated with MVDs in CRC tissues (Pearson coefficient r = 0.580, p = 0.01). The cells culture supernatant of CRC cell with miRNA-92a overexpression (or suppression) can promoted (or reduced) the formation of HUVEC tubules (P <0.05). Elevated miRNA-92a expression was associated with reduced PTEN expression in CRC cells (p <0.01). Conclusion: Modulation of miR-92a, which is highly expressed in CRC cells and tissues, is associated directly with differences in CRC angiogenesis. MiR-92a could promote tumor angiogenesis in CRC by inhibiting the expression of PTEN.

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 998
Author(s):  
Maria Latacz ◽  
Jadwiga Snarska ◽  
Elżbieta Kostyra ◽  
Konrad Wroński ◽  
Ewa Fiedorowicz ◽  
...  

Colorectal cancer (CRC) is the third most commonly occurring cancer worldwide. Intestinal cells are CYP27B1 gene expression sites and, as a consequence, they are capable of converting pro-vitamin D into the active paracrine and autocrine forms. It was demonstrated that rs10877012 polymorphism in the CYP27B1 gene influenced the circulating vitamin D level. This provided a rationale for determining the role that this polymorphism plays in the risk of developing colon cancer. In this study, we investigated the association of rs10877012 (T/G) polymorphism in the CYP27B1 gene with CRC susceptibility. The study population (n = 325) included CRC patients (n = 106) and healthy controls (n = 219). DNA was extracted from peripheral leukocytes and analyzed for the CYP27B1 polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. We found an association between the presence of the T allele at the polymorphic site (odds ratio (OR) = 2.94; 95% CI 1.77–4.86; p < 0.0001) and a decreased CRC incidence.


2018 ◽  
Vol 33 (4) ◽  
pp. 401-406 ◽  
Author(s):  
Qizhao Ma ◽  
Zhigang Mao ◽  
Jipei Du ◽  
Shiping Liao ◽  
Yanjiang Zheng ◽  
...  

Background: Previous studies have reported that polymorphisms in the interleukin-1 gene may be involved in tumorigenesis and tumor progression. Aim: The purpose of the present study was to evaluate whether an insertion/deletion polymorphism, rs3783553, located in the miR-122 target gene interleukin-1α, was associated with the risk of colorectal cancer. Methods: Genomic DNA was extracted from peripheral venous blood of 382 patients with colorectal cancer and 433 controls, and the polymorphism was genotyped using a polymerase chain reaction assay. Results: Significantly decreased colorectal cancer risk was observed to be associated with the interleukin-1α rs3783553 insertion/insertion genotype ( P=0.0001; OR=0.41; 95% CI 0.26, 0.65) and the insertion allele ( P<0.001; OR=0.68; 95% CI 0.55, 0.83). Stratification analysis based on clinical and pathological features also revealed that the “TTCA” insertion allele of rs3783553 contributes to slow the progression of colorectal cancer. Conclusion: These results suggest that the rs3783553 polymorphism could be a useful genetic marker to predict the size/extent of colorectal cancer.


2019 ◽  
Author(s):  
Ayat B. Al-Ghafari ◽  
Areej M. Alqahtani ◽  
Suzan N. Alturki ◽  
Huda Abdulaziz Al Doghaither ◽  
Hanaa M. Tashkandi ◽  
...  

Abstract Background Multidrug resistance member 1 (MDR1) is located on chromosome 7 and encodes P-glycoprotein (Pgp), which is universally accepted as a drug resistance biomarker. MDR1 polymorphisms may change either the protein expression or function, suggesting its possible association with cancers, including colorectal cancer (CRC). Thus, this study aimed to determine the effects of MDR1 polymorphisms on the drug response of Saudi CRC patients.Methods DNA samples were obtained from 62 CRC patients and 100 healthy controls. The genotypes and allele frequencies of the MDR1 polymorphisms G2677T and T1236C were determined by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP).Results No significant difference was observed in the genotype distribution and allele frequency of T1236C between the CRC the patients and the controls. However, G2677T was found to play a highly significant protective role against the progression of CRC. Moreover, the results showed that none of the genotypes in SNPs T1236C and G2677T affected chemoresistance to Xeliri and Xelox.Conclusions T1236C in the MDR1 gene is not related to CRC risk, and G2677T protects against the development of CRC. Both MDR1 polymorphisms are not associated with the risk of chemoresistance.


Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769226 ◽  
Author(s):  
Reza Nedaeinia ◽  
Mohammadreza Sharifi ◽  
Amir Avan ◽  
Mohammad Kazemi ◽  
Abdolreza Nabinejad ◽  
...  

Colorectal cancer is among the most lethal of malignancies, due to its propensity to metastatic spread and multifactorial-chemoresistance. The latter property supports the need to identify novel therapeutic approaches for the treatment of colorectal cancer. MicroRNAs are endogenous non-coding small RNA molecules that function as post-transcriptional regulators of gene expression. Recently, programmed cell death 4 has been identified as a protein that increases during apoptosis. This gene is among the potential targets of miR-21 (OncomiR). Locked nucleic acid–modified oligonucleotides have recently emerged as a potential therapeutic option for targeting microRNAs. The aim of this study was to explore the functional role of locked nucleic acid-anti-miR-21 in the LS174T cell line in vitro and in vivo models. LS174T cells were treated with locked nucleic acid-anti-miR-21 for 24, 48, and 72 h in vitro. The expression of miR-21 and PDCD4 at messenger RNA (mRNA) level was evaluated by quantitative real-time polymerase chain reaction, while the protein level of PDCD4 was determined by Western blotting. Cell migratory behavior and the cluster-forming ability of cells were assessed before and after therapy. The disseminated tumor cells were assessed in the chick chorioallantoic membrane model by Alu quantitative polymerase chain reaction. Locked nucleic acid-anti-miR-21 was transfected successfully into the LS174T cells and inhibited the expression of miR-21. Locked nucleic acid-anti-miR-21 inhibited the migration and the number of cells forming clusters. Moreover, we found that locked nucleic acid-anti-miR-21 transfection was associated with a significant reduction in metastatic properties as assessed by the in ovo model. Our findings demonstrated the novel therapeutic potential of locked nucleic acid-anti-miR-21 in colon adenocarcinoma with high miR-21 expression.


1995 ◽  
Vol 109 (2) ◽  
pp. 465-471 ◽  
Author(s):  
Lynn Cawkwell ◽  
Ding Li ◽  
Fraser A. Lewis ◽  
Iain Martin ◽  
Michael F. Dixon ◽  
...  

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