Background: ARID1A has been described as a tumor suppressor gene, participating in chromatin re-modeling, epithelial-mesenchymal-transition and many other cellular and molecular processes. It has been cited as a contribute in tumorigenesis. The role of ARID1A in CRC is not yet defined. Aim: To investigate the role of ARID1A methylation and CNV in its expression in CRC cell lines and to examine the relationship between ARID1A status with survival and clinicopathologic characteristics in patients with CRC. Methods: We used RT-PCR to determine both CNV and expression of ARID1A from six CRC cell lines. We used MSP to evaluate methylation of ARID1A. IHC was used to assess ARID1A protein expression. We also evaluated MSI and EMAST status in 18 paired CRC and adjacent normal tissues. 5AzadC was used to assess effect of DNA demethylation on ARID1A expression. Statistical analysis was performed to establish correlations between ARID1A expression and other parameters. Results: Among the 18 CRC tumors studied, 7 (38.8%) and 5 tumors (27.7%) showed no or low ARID1A expression, respectively. We observed no significant difference in ARID1A expression for overall patient survival, and no difference between clinicopathological parameters including MSI and EMAST. However, lymphatic invasion was more pronounced in the low/no ARID1A expression group when compared to moderate and high expression group (33% VS. 16.6% respectively. ARID1A promoter methylation was observed in 4/6 (66%) cell lines and correlated with ARID1A mRNA expression level ranging from very low in SW48, to more pronounced in HCT116 and HT-29/219. Treatment with the methyltransferase inhibitor 5-Azacytidine (5-aza) resulted in a 25.4-fold and 6.1-fold increase in ARID1A mRNA expression in SW48 and SW742 cells, respectively, while there was no change in SW480 and LS180 cells. No ARID1A CNV was observed in the CRC cell lines. Conclusion: ARID1A expression is downregulated in CRC tissues which correlates with it being a tumor suppressor protein. This finding confirms ARID1A loss of expression in CRC development. Our in-vitro results suggest high methylation status associates with reduced ARID1A expression and contributes to CRC tumorigenesis. However, there was no significant association between ARID1A loss of expression and clinicopathological characteristics. Future in-vivo analysis is warranted to further establish ARID1A role in colorectal neoplastic transformation.
BackgroundThyroid cancer (TC) is known to be the most common endocrine malignancy with an incidence rate which has increased by 2.3-fold over the past 30 years. Approximately, 30% of the thyroid fine-needle aspiration biopsy (FNAB) outcomes are indecisive. Moreover, researchers recognized multiple differentially expressed microRNAs (miRNAs) as candidate diagnostic markers for thyroid nodules. The purpose of this study was to identify thyroid tumor-associated miRNAs in FNAB with the capacity to be developed as unique biomarkers.Materials and methodsAccording to the study design, a quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) was applied to evaluate the expression levels of nine miRNAs (Let7, miR-34a, miR-146b, miR-221, miR-151, miR-155, miR-181b, miR-222 and miR-375) among 224 FNA samples as the training set.ResultsThe findings of this study revealed that miR-181b and miR-146b are the best predictors to diagnose benign thyroid FNA samples from malignant samples. However, the remaining miRNAs were co-expressed and had no significant effect on the predictor model. On the other hand, sensitivity and specificity of miR-181b and miR-146b were reported at 83.0%–83.0% and 83.0%–66.0%, respectively.ConclusionsAccording to the results of this study, miR-146b and miR-181b might be considered as adjunct markers contributing to thyroid FNAB in tumor types. In addition, miR-146b and miR-181b were recognized as biomarkers for discriminating benign thyroid nodules from malignant ones. It is suggested that further prospective clinical trials be conducted to evaluate the accuracy of such findings in a larger cohort and determine the clinical uses.
Background: ARID1A has been described as a tumor suppressor gene, participating in chromatin re-modeling, epithelial-mesenchymal-transition and many other cellular and molecular processes. It has been cited as a contribute in tumorigenesis. The role of ARID1A in CRC is not yet defined. Aim: To investigate the role ARID1A methylation and CNV in its expression in CRC cell lines and to examine the relationship between ARID1A status with survival and clinicopathologic characteristics in patients with CRC. Methods: We used RT-PCR to determine both CNV and expression of ARID1A from six CRC cell lines. And used MSP to evaluate methylation of ARID1A. We used (IHC) to ARID1A protein expression, and, evaluate both MSI and EMAST status in 18 paired CRC and adjacent normal tissues. Statistical analysis was performed to establish correlations between ARID1A expression and other parameters. Results: Among the 18 CRC tumors studied, 7 (38.8 %) and 5 tumors (27.7%) showed no or low ARID1A expression, respectively. We observed no significant difference in ARID1A expression for overall patient survival, and no difference between clinicopathological parameters including MSI and EMAST. However, lymphatic invasion was more pronounced in the low/no ARID1A expression group when compared to moderate and high expression group (33% VS. 16.6% respectively. ARID1A promoter methylation was observed in 4/6 (66%) of cell lines and correlated with ARID1A mRNA expression level ranging from very low in SW48, to more pronounced in HCT116 and HT-29/219. Treatment with the methyltransferase inhibitor 5-Azacytidine (5-aza) resulted in a 25.4-fold and 6.1-fold increase in ARID1A mRNA expression in SW48 and SW742 cells, respectively, while there was no change in SW480 and LS180 cells. No ARID1A CNV was observed in the CRC cell lines. Conclusion: ARID1A expression is downregulated in CRC tissues correlate with it being a tumor suppressor protein. This finding confirms ARID1A loss of expression in CRC development. Our in-vitro results suggest high methylation status associates with reduced ARID1A expression and contribute to CRC tumorigenesis. There was no significant association between the ARID1A loss of expression and clinicopathological characteristics. ARID1A might be a useful biomarker for colorectal cancer. Future in- vivo analysis is warranted to further established this role. Citation Format: Mehran Erfani, Seyed Vahid, Maral Mokhtari, Mozhdeh Zamani, Kamran Tahmasebi, Mahvash Alizadeh, Alireza Taghavi, John Carethers, Minoru Koi, Hassan Brim, Pooneh Mokarram, Hassan Ashktorab. Altered ARID1A expression in colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 294.
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