Metformin and long non-coding RNAs in breast cancer.

Breast cancer (BC) is the second most common cancer and cause of death in women. In recent years many studies investigated the association of long non-coding RNAs (lncRNAs), as novel genetic factors, on BC risk, survival, clinical and pathological features. Recent studies also investigated the roles of metformin treatment as the firstline treatment for type 2 diabetes (T2D) played in lncRNAs expression/regulation or BC incidence, outcome, mortality and survival, separately. This comprehensive study aimed to review lncRNAs associated with BC features and identify metformin-regulated lncRNAs and their mechanisms of action on BC or other types of cancers. Finally, metformin affects BC by regulating five BC-associated lncRNAs including GAS5, HOTAIR, MALAT1, and H19, by several molecular mechanisms have been described in this review. In addition, metformin action on other types of cancers by regulating ten lncRNAs including AC006160.1, Loc100506691, lncRNA-AF085935, SNHG7, HULC, UCA1, H19, MALAT1, AFAP1-AS1, AC026904.1 is described.

Association of ACE gene polymorphisms with in-stent restenosis by stent type (biomime, supraflex, xience).

INTRODUCTION: Angiotensin Converting Enzyme or ACE is an exo-peptidase that causes the conversion of angiotensin I to angiotensin II, vasoconstriction, and aldosterone production. ACE gene polymorphism (I/D) affects enzyme activity and the risk of coronary artery disease or CAD. AIMS: To examine the role of ACE (I/D) Gene Polymorphisms by Stent Types (Biomime, Supraflex, Xience) the Ace gene allele and genotype frequencies were determined in patients who underwent angioplasty. MATERIAL & METHODS: Patients with in-stent restenosis (ISR+) (N = 53) and patients as non-ISR group (ISR-) (N = 68) have been enrolled in this study based on follow-up angiography > 1 year after PCI. Frequencies of allele and genotypes of the ACE (I/D) variant were determined using polymerase chain reaction (PCR). RESULTS: The genotypes and allele frequencies were not significantly different between the studied populations (p-Values > 0.05). However, there was a significant difference between people with a history of Clopidogrel use in the ISR- and ISR + groups observed (p-Values > 0.005). CONCLUSION: In the present study, there was no statistically significant relationship between ACE (I/D) gene polymorphism and the incidence of restenosis in patients who underwent repeat angiography. The results showed that the number of patients who received Clopidogrel in the ISR + group was significantly less than the ISR- group. This issue can indicate the inhibitory effect of Clopidogrel in the recurrence of stenosis.

Investigating the relationship between the VNTR variant of the interleukin-1 receptor antagonist gene and coronary in-stent restenosis.

OBJECTIVE: This study aimed to examine the association between the interleukin-1 receptor antagonist gene (IL-1RN) and coronary in-stent restenosis (ISR) through the analysis of the VNTR variant based on the previously reported results. MATERIALS AND METHODS: The samples were classified into two clearly defined groups: the case group, which comprised 45 patients diagnosed with in-stent restenosis (ISR+), and the control group, which included 60 patients without ISR (ISR-). Polymerase chain reaction (PCR) was performed to examine the 86-bp VNTR variant of the IL-1RN gene. RESULTS: In the analysis of six identified groups consisting of variant alleles of 86 base pairs of VNTR of the IL-1RN gene statistically significant difference was observed for the presence of IL1RN*2 allele between cases and controls (p = 0.04, OR; 0.045). CONCLUSION: Individuals with allele 2 of the IL-1Ra gene may be more predisposed to ISR. This could be due to an imbalance between IL-1Ra and IL-1ß which is crucial in preventing the initiation or advancement of inflammatory diseases in specific organs. The observed phenomenon can be characterized by increased production of IL-1ß and potential reduction of IL-1Ra as a result of functional VNTR variation in IL-RN gene.

The vitamin D receptor gene variants, ApaI, TaqI, BsmI, and FokI in diabetic foot ulcer and their association with oxidative stress.

INTRODUCTION: To date, numerous disorders have been linked to vitamin D deficiency. Several lines of evidence indicate a relationship between vitamin D deficiency and the risk of developing type 2 diabetes. It has been postulated that vitamin D may influence insulin activity, which can predispose individuals to develop type 2 diabetes. MATERIALS AND METHODS: In this case-control study, 262 patients with definite type 2 diabetes were enrolled, considering whether they were being affected by diabetic foot ulcers or not. The plasma levels of vitamin D and homocysteine were measured using ELISA, and the PCR-RFLP technique was utilized to determine allele and genotype frequencies. The antioxidant capacity of plasma samples of diabetic patients was analyzed using the thiobarbituric acid reactive substance (TBARS) and ferric reducing ability of plasma (FRAP) assays. RESULTS: The obtained results demonstrated no significant difference in the frequency of TaqI and BsmI polymorphisms between the case and control groups. However, the frequency of genotypes and alleles of the ApaI polymorphism in the VDR gene significantly differed between the case and control groups. A significant correlation was found between ApaI polymorphism and oxidative stress, as patients with the GG genotype had lower levels of TBARS than those with other genotypes. Furthermore, in the case group, patients with the CC genotype of BsmI showed a significant decrease in TBARS levels. DISCUSSION: It seems that the plasma levels of vitamin D do not differ between patients with or without diabetic foot ulcers; however, the presence of some VDR gene polymorphisms is thought to be involved in the development of diabetic foot ulcers via increasing oxidative stress.

PTEN promoter methylation and expression in endometrial cancer tissues.

Introduction: Some gene expression regulation in cancers can be controlled by epigenetic change like methylation. PTEN promoter methylation and expression were evaluated in endometrial cancer. Methods: The study was run on 39 tumor tissues of endometrial cancer patients and 41 normal endometrial tissues. After total RNA extraction, cDNA synthesis was done by reverse transcription of the total (real-time PCR) using SYBER Green master mix. DNA extraction and bisulfite treatment were conducted and methylation was semiquantified by the methylation-sensitive high-resolution melting method. Finally, promoter methylation quantification of the total number of 25 tumors and 22 non-neoplastic tissues was done. Results: PTEN gene expression showed a significant decrease in endometrial cancer tissues. Promoter methylation was significantly lower in the non-neoplastic group (7.2; p < 0.001). In addition, PTEN promoter methylation was observed in 52.0% of tumor tissues compared with 13.6% in the non-neoplastic group (p = 0.06). There were no significant correlations between PTEN expression and methylation and clinicopathological features in endometrial cancer patients (p > 0.05). Conclusion: PTEN gene expression in endometrial cancer tissues decreased because of its promoter hypermethylation.

Investigating the association of matrix metalloproteinase-2 gene variants with endometriosis in an Iranian population.

OBJECTIVES: matrix metalloproteinases including matrix metalloproteinase-2 play a key role in endometrial extra cellular matrix breakdown in endometriosis. Aberrant expression of matrix metalloproteinase-2 has been reported in eutopic and ectopic endometrial tissue of endometriosis patients so altered expression of matrix metalloproteinase-2 due to polymorphisms may lead to establishment and progression of endometriosis. In this study the association between -735 C/T (rs2285053) and -1575 G/A (rs243866) variants of matrix metalloproteinase-2 gene with presence of endometriosis in an Iranian population were investigated for the first time. STUDY DESIGN: A case-control association study was conducted to investigate the role of MMP-2-735 C/T and _1575 G/A variants in development of endometriosis. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine genotype frequencies of these variants in 100 endometriosis patients and 200 normal samples. Total genomic DNA was extracted from blood samples and single-nucleotide polymorphism flanking regions were amplified using designed specific primers. Enzymatic digestion was performed using Pag I and Hinf I restriction enzymes for rs2285053 and rs243866 variants, respectively. Statistical analysis was ascertained using statistical package for social science version 16 and "SHEsis" software. RESULTS: There were no significant differences in genotype frequencies of rs2285035 (-735C/T) variant between case and control groups (CC + CT vs. TT p = 0.40; OR = 0.50, 95 % CI 0.100-2.551). There were also no significant differences for C allele frequencies in both case and control groups (p = 0.9). For variant rs243866 (-1575 G/A) the differences in genotype frequencies between case and controls group were determined to be significant (GG + GA vs. AA p = 0.041; OR = 6.46, 95 % CI 0.82-50.43). The frequency of G allele was significantly different in case and control groups (p = 0.037). CONCLUSION: In conclusion, existence of rs243866 variant in promoter region of matrix metalloproteinase-2 gene can increase the risk of endometriosis in Iranian women.