MIRNA-mediated regulation of the PI3K/AKT signaling pathway in colorectal cancer: A study based on data mining

Aim: In colorectal cancer (CRC), expression of genes involved in the PI3K/Akt signaling pathway varies significantly. Studies haveshown that microRNAs (miRNA) have important roles in the development of CRC. Accordingly, the aim of this study was to determinemiRNAs affecting the critical genes in the PI3K/Akt pathway by analysis of The Cancer Genome Atlas (TCGA) CRC data sets and toevaluate the clinical significance of these miRNAs.Material and Methods: Initially, CRC mRNA, miRNA expression levels and patient data were obtained from TCGA database. The studyincluded 220 CRC patients. MiRNAs that were negatively correlated with genes in the PI3K/Akt signaling pathway were selected, andtheir expression levels were compared with the clinical and demographic characteristics of CRC patients.Results: miR-18a, miR-19b, miR-17, miR-106b, miR-130b and miR-135b were found to be negatively correlated with genes that playkey roles in the PI3K/Akt pathway. Also, miR-18a, miR-19b, miR-17 and miR-135b were found to vary significantly according to theCRC subtype.Conclusion: Consequently, the PI3K/Akt signaling pathway was found to be deregulated in CRC and the majority of genes involved inthis signaling pathway were associated with miRNAs. Thus, PI3K/Akt miRNA axis might serve as a potentially distinctive diagnostic,prognostic and therapeutic avenue against CRC

Uzun Kodlamayan RNA NORAD’ın Mitomisin C İlişkili Kemorezistansta Olası Rolü

Amaç: Non-coding RNA activated by DNA damage (NORAD), deoksiribo nükleik asit (DNA) hasarı cevabı sırasında aktive olan bir uzun kodlamayan ribonükleik asittir (RNA). Çalışmalar, NORAD’ın insan kanserlerinde aşırı eksprese edildiğini ve ilaca bağlı kemorezistans ile ilişkili olduğunu göstermektedir. Bu çalışma, mitomisin C ile ilişkili kemorezistans ve mitomisin C ile indüklenen DNA hasar yanıtı sırasında spesifik olarak aktive edilen bir uzun kodlamayan RNA NORAD’ın olası rolünü araştırmayı amaçlamaktadır. Gereç ve Yöntem: Hücre kültürü deneylerinde MDA-MB-231 meme kanseri hücreleri kullanıldı. Mitomisin C’nin meme kanseri hücreleri üzerindeki etkilerini belirlemek için MTT hücre canlılığı testi kullanıldı ve uygulama dozu buna göre belirlendi. NORAD gen ekspresyon düzeylerinin analizi için kantitatif qPCR yöntemi kullanıldı. Bulgular: Mitomisin C’nin meme kanseri hücrelerinin hücre canlılığını doza bağlı olarak baskıladığı ve yarı-maksimum inhibisyon konsantrasyonunun 1,12 µg/mL olduğu belirlendi (p<0,0001). Özellikle, mitomisin C ile muamele edilen meme kanseri hücrelerinde NORAD’ın önemli bir farklı aktivasyonu belirlendi (p<0,0001). Sonuç: Burada elde edilen bulgular, mitomisin C ile ilişkili kemoresistans ve mitomisin C ile indüklenen DNA hasar yanıtında NORAD’ın olası rolünün olabileceğini göstermektedir

Deregulation of Cancer-Associated Genes in Odontogenic Cysts

Objectives: The aim of the present study was to demonstrate the key role of differential expression levels of RB1, TP53, XIAP, BCL2 AIFM3, BAX, CASP3 and CASP9 genes in odontogenic cysts. Materials and Methods: A total number of 15 patients who diagnosed with odontogenic cyst were enrolled for the present study. For the quantitative gene expression analysis, cyst and adjacent gingival healthy tissues of patients were collected during surgical assessments. Quantitative analysis of gene expression levels RB1, TP53, XIAP, BCL2 AIFM3, BAX, CASP3 and CASP9 were achieved real-time PCR method. For the optimization of gene expression levels GAPDH reference gene was used. Results: Expression of both RB1 and TP53 genes were markedly diminished in odontogenic cysts tissues as compared to healthy tissues (p&lt;0.05). Likewise, levels of CASP3 and CASP9 genes were found to be significantly reduced in odontogenic cysts tissues compared to healthy tissues (p&lt;0.05). In contrast, expression levels of XIAP was significantly elevated (p&lt;0.05). Although BCL2, AIFM3, and BAX genes were also differentially expressed in odontogenic cysts tissues, these variations were statistically insignificant (p&gt;0.05).  Conclusions: The findings of the present study indicates that RB1, TP53, XIAP, CASP3 and CASP9 genes might have chief roles in formation odontogenic cysts and responsible for the increased cell proliferation in these tissues

The role of hepcidin and its related genes (BMP6, GDF-15, and HJV) in rats exposed to ischemia and reperfusion

Background/aim: To determine the roles of hepcidin and its related genes in a renal ischemia/reperfusion model. Materials and methods: A total of 20 Wistar albino rats were equally divided into 2 groups: Group I was the control group and Group II was the ischemia and reperfusion (I/R) group (60 min of ischemia + 48 h of reperfusion). I/R was performed on the left kidneys of these rats and then the I/R-treated kidneys were removed. The levels of serum biochemical markers were evaluated after renal I/R. The expression levels of hepcidin-linked genes [growth differentiation factor 15 (GDF-15), bone morphogenetic protein 6 (BMP6), and hemojuvelin (HJV)] were also measured by RT-PCR technique. In addition, the tissues were evaluated histopathologically. Results: No significant association was found between renal dysfunction and I/R when compared to biochemical parameters (P &gt; 0.05). However, differences in platelet values were statistically significant (P &lt; 0.05). Expression levels of GDF-15, BMP6, and HJV genes increased, but this increase was not statistically significant. In addition, histopathological evaluation was performed using hematoxylin and eosin stain. This showed a significant relationship between the control group and I/R group for ischemic and nonischemic kidney scoring. Conclusion: Hepcidin and BMP6, HJV, and GDF-15 should be taken into account when investigating the process of I/R.Background/aim: To determine the roles of hepcidin and its related genes in a renal ischemia/reperfusion model. Materials and methods: A total of 20 Wistar albino rats were equally divided into 2 groups: Group I was the control group and Group II was the ischemia and reperfusion (I/R) group (60 min of ischemia + 48 h of reperfusion). I/R was performed on the left kidneys of these rats and then the I/R-treated kidneys were removed. The levels of serum biochemical markers were evaluated after renal I/R. The expression levels of hepcidin-linked genes [growth differentiation factor 15 (GDF-15), bone morphogenetic protein 6 (BMP6), and hemojuvelin (HJV)] were also measured by RT-PCR technique. In addition, the tissues were evaluated histopathologically. Results: No significant association was found between renal dysfunction and I/R when compared to biochemical parameters (P &gt; 0.05). However, differences in platelet values were statistically significant (P &lt; 0.05). Expression levels of GDF-15, BMP6, and HJV genes increased, but this increase was not statistically significant. In addition, histopathological evaluation was performed using hematoxylin and eosin stain. This showed a significant relationship between the control group and I/R group for ischemic and nonischemic kidney scoring. Conclusion: Hepcidin and BMP6, HJV, and GDF-15 should be taken into account when investigating the process of I/R

The Investigation of Antidiabetic Effects of Leontice leontopetalum Extract on Human Pancreatic β Cell Lines (1.1B4) Treated with Streptozotocin

One of the alternative therapeutic methods is herbal medicine. Leontice leontopetalum belongs to Berberidaceae family. The aim of study was investigated the extract of LL on human pancreatic beta cell-treated with STZ. Materials and methods: The human pancreatic beta cell (1.1B4) line was used the current study. LL’s extracts (1, 10, 100, and 1000 ug/ml) were supplemented in media for twenty-four hours and/or after STZ treatment (10 and 20 mM). Cells survivals (MTT), cells proliferation were shown by using xCelligence. Insulin content and releasing were measured at 1.1, 8.4 and 16.7 mM glucose concentrations. Results: The result of MTT was shown that cell survival was decreased, based on dose-dependent. When looked at xCelligence results, cell proliferation in STZ groups and the lowest and highest concentrations of LL were attenuated in a dose-dependent manner. Also, cotreatments of LL and STZ were decreased as well. The result of insulin-releasing on glucose induction was shown that STZ concentration gave rise to reduce insulin content at low and high glucose levels. Also, co-treatment of LL and STZ attenuated insulin content based on dose. Conclusion: It was considered that LL treatment led to increased insulin realizing, resulting from decreasing insulin content in diabetic beta cells, but decrease cell survival

The Anticancer Activity of Cetraria Islandica (L.) Ach in Breast Cancer Cells Through Crosstalk of Ampk-α1 and Erk1/2 Signalling

In the present study, we aimed to evaluate the anticancer activities of Cetraria islandica (C.islandica) extracts on MCF-7 breast cancer cell lines. Cell viability, protein levels, apoptotic cells number, F-actin distribution were measured. Cell viability of MCF-7 breast cancer cells was found to be reduced in a dose-dependent manner.EC50 values of C.islandica on MCF-7 cells were found to be 9.2047 E-5 g/ml (cell amount) by using intelligence system. Expressions of p53, caspase 3 and Bcl-2, were shown to be elevated after low doses of extract and diminished after high dose treatments. PPAR- protein level was decreased, although AMP-activated kinases-α1 (AMPK-α1) protein level was increasedin its extract groups. ERK1/2 protein level was also elevated in its extract groups. 125 mg/ml of extract treated cells show a low decrease in actin filament density. MCF-7 cells with C.islandica treatment for 24 h increased the apoptotic cell percentage, though the cells-treated with C.islandica for 48 was high necrotic cells percentage. Consequently, the C.islandica extract treatment causes to elevate ERK1/2 and AMPK-α1 protein levels, resulting in PPAR- and then triggers the apoptosis by modulation caspase-3 and P53 protein levels. Therefore, C.islandica might be a good candidate for anticancer tissue, especially soft tissue tumours

Cross-regulation of non-coding RNAs and their correlations with target protein-coding genes in CRC pathobiology

Illuminating the correlations between non-coding RNAs and protein-coding genes are of great interest to understand more about the molecular mechanisms that drive malignant transformation and understanding such correlations will enable development of more specific and efficient targeted therapeutics. Accordingly, in this comprehensive meta-analysis study, we tried to determine correlations between long non-coding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) molecules that are involved in the pathogenesis of colorectal cancer (CRC). For the present study, current colorectal cancer studies published until 20 August 2017 and associated with the lncRNA-miRNA-mRNA interactions was included. The current literature search was done online in Pubmed, Embase and Web of Science databases. These databases have been screened with three keywords; “lncRNA” “miRNA” and “colorectal cancer”. As a result, colorectal neoplasia differentially expressed (CRNDE) was determined to be consistently up-regulated in CRC tissues and inversely associated with miR-181a-5p. Also, CRNDE expression was significantly associated with lymph node metastasis (p = 0.032). Additionally, a significant association was determined between CRC and survival time in the OS analysis of FER1L4, TUSC7, UCC and lincRNA-ROR. More importantly, there was a negative correlation between lncRNA-miRNA expressions (p = 0.001). Particularly, CRNDE/miR-181a-5p, FER1L4/miR-106a-5p, TUSC7/miR-211, UCC/miR-143 and lincRNA-ROR/miR-145 was negatively correlated. In addition, there was a significant positive correlation between GAPLINC/CD44 and TUSC7/CDK6 in CRC tissues (p = 0.000). Overall analysis showed that lncRNAs and mRNAs, which are targets of the same miRNA, have positive interactions. In addition, miRNAs were shown to have negative correlations with target lncRNA/mRNA. © 2018 Elsevier B.V

The Dimensions of the Relationship Between Economy and Divorce in Turkey: Application on Border Provinces (Gaziantep-Kilis-Hatay-Şanlıurfa)

Turkey, especially after the 1980s, began to adopt a liberal economic policy alongside the impact of globalization. The 1980s are known as the years when countries around the world liberalized their economies and opened up to the global market. During this era of globalization, there was a significant momentum in the economic development of countries worldwide, leading to the creation of new employment opportunities. However, due to regional and global political developments, migration movements were accelerated.As a result, the challenging economic conditions caused adverse effects on families. Statistical analysis data from Gaziantep, Kilis, Hatay, and Şanlıurfa provinces indicate that both the economic conditions and education levels of migrating individuals have negatively influenced divorce rates. Keywords: Migration, Economy, Divorce DOI: 10.7176/JESD/14-14-02 Publication date:August 31st 202

Enhanced E2F1 activity increases invasive and proliferative activity of breast cancer cells through non-coding RNA CDKN2B-AS1

Long non-coding RNAs have recently appeared as fundamental regulators of gene transcription in several biological processes, but only a few have known functional influences in the malignant transformation of breast cancer. CDKN2B-AS1 gene, also termed ANRIL, encoding a long non-coding RNA is located in the CDKN2B-CDKN2A gene cluster, loss of which is the most frequent alternation in several types of human malignancies. CDKN2B-AS1 is involved in the suppression of tumor suppressor genes (INK4a, ARF, and INK4b) and has been recognized as a direct target of E2F1. However, the roles of E2F1–CDKN2B-AS1 interaction in breast cancer have remained muchly mysterious. In this particular study, we reveal that both CDKN2B and CDKN2B-AS1 genes were differentially expressed in breast cancer cells in contrast to breast epithelial cells. Ectopic expression of E2F1 activated CDKN2B-AS1 but not CDKN2B expression. Lastly, overexpression of E2F1 improved the colony formation and migratory capacities of breast cancer cells. These results suggest that enhanced E2F1 activity increased invasive and proliferative activity of breast cancer but not breast epithelial cells possibly through up-regulating CDKN2B-AS1 transcript. © 2020 Elsevier B.V

ARID3A-mediated modulation of TP73 and TP73-AS1 in osteosarcoma cells

Osteosarcoma is the most common primary malignancy arising from bone. Increasing mass of indications suggest that long non-coding RNAs (lncRNAs) play crucial roles in the development of progressions of human cancers including osteosarcoma. Although several lncRNAs have shown to be involved in the molecular pathogenesis of osteosarcoma, identification of novel lncRNAs involved in the osteosarcoma pathobiology remained muchly elusive. Besides, ARID3A is a member of ARID family of DNA binding proteins. ARID3A was also implicated in osteosarcoma pathogenesis. Accordingly, in the present study, we mechanistically investigated the effect of ARID3A on the expression of TP73 and TP73-AS1 in osteosarcoma cells and to determine the relationship between them. For the overexpression of ARID3A in U2-OS cells, pER_xpress_ARID3A expression vector and for the silencing of ARID3A, ARID3A-spesific siRNA was used. Expression levels of ARID3A, TP73 and TP73-AS1 genes were determined by qPCR method. As a result, expression levels of TP73-AS1 were well-correlated with the ARID3A expression levels whereas TP73 expression levels were not well-correlated with ARID3A. In conclusion, our results indicate that ARID3A might be involved in the regulation of TP73-AS1 in osteosarcoma. To our knowledge, this is the first study revealing the role of ARID3A in the regulation of TP73 and TP73-AS1 genes. © 2020 Elsevier Inc