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Identification of a novel interplaying loop of PPARγ and respective lncRNAs are involved in colorectal cancer progress
International Journal of Biological Macromolecules ( IF 7.7 ) Pub Date : 2022-08-05 , DOI: 10.1016/j.ijbiomac.2022.07.247
Maral Hajipour 1 , Khatereh Mokhtari 1 , Mohammad Mahdevar 2 , Maryam Esmaeili 2 , Maryam Peymani 3 , Mohammad Hossein Nasr-Esfahani 2 , Sepideh Mirzaei 4 , Mehrdad Hasehmi 5 , Kiavash Hushmandi 6 , Kamran Ghaedi 7
Affiliation  

Long noncoding RNAs (lncRNAs) as regulatory molecules play important roles in early treatment and diagnosis of cancers. Considering the role of PPARγ in colorectal cancer (CRC) as a tumor suppressor, the GEO database was used to identify candidate genes that affect the activation of PPARγ protein in CRC cell lines. Then were selected 5 genes containing PPARγ response element (PPRE) in up to 4000 bp upstream and were affected by PPARγ protein activation in HT-29 colon cancer cell line using UCSC database. Expression meta-analysis was applied to map the expression network between candidate genes and all known lncRNAs through expression correlation and lncRNAs that correlated with a greater number of candidate genes (R > 0.5, P.value < 0.001). Moreover, were selected 3 lncRNAs as lncRNAs affected by PPARγ protein activation. Next, the expression levels of candidate genes and lncRNAs were evaluated using RT-qPCR in HT-29 cell line. Results showed a significant increase (FDR <0.05) in the expression level of 5 candidate genes and lncRNAs LINC01133, MBNL1-AS, LOC100288911 after treatment with pioglitazone as PPARγ ligand compared to the untreated group in HT-29 cells. Although additional tests are needed to confirm bioinformatics predictions, it can be concluded that increased expression of PPARγ may increase genes and lncRNAs expression. In summary, this study could be suggested identifying lncRNAs affected by PPARγ activation could be a new strategy in understanding the function and activity of PPARγ in colon cancer.



中文翻译:

鉴定 PPARγ 和各自 lncRNA 的新相互作用环与结直肠癌进展有关

长链非编码 RNA (lncRNA) 作为调控分子在癌症的早期治疗和诊断中发挥着重要作用。考虑到PPARγ在结直肠癌 (CRC) 中作为肿瘤抑制因子的作用,GEO 数据库被用于识别影响CRC 细胞系中PPARγ蛋白活化的候选基因。然后使用UCSC数据库在HT-29结肠癌细胞系中选择5个上游含有高达4000 bp的PPARγ反应元件(PPRE)并受PPARγ蛋白活化影响的基因。表达荟萃分析通过表达相关性和与更多候选基因相关的lncRNA(R> 0.5,P值 < 0.001)。此外,选择了 3 个 lncRNA 作为受PPARγ蛋白激活影响的 lncRNA。接下来,使用 RT-qPCR 在 HT-29 细胞系中评估候选基因和 lncRNA 的表达水平。结果显示,与未处理组相比,HT-29 细胞中用吡格列酮作为PPARγ配体处理后,5 个候选基因和 lncRNA LINC01133MBNL1-ASLOC100288911的表达水平显着增加(FDR <0.05) 。虽然需要额外的测试来确认生物信息学的预测,但可以得出结论,PPARγ的表达增加可能会增加基因和 lncRNAs 的表达。综上所述,本研究表明,鉴定受PPARγ激活影响的 lncRNA 可能是了解PPARγ在结肠癌中的功能和活性的新策略。

更新日期:2022-08-05
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