醛固酮瘤中长链非编码RNA的差异表达及功能分析
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摘要
目的研究在醛间酮瘤中有差异表达的长链非编码RNA (Long non-coding RNA,lncRNA)并初步分析后者在醛同酮瘤发生发展中的作用。方法通过基因芯片筛选醛固酮瘤中瘤体相对于瘤旁有差异表达的lncRN A,通过分析得出目标lncRN A,并使用RT-qPCR对目标lncRNA的表达情况进行验证,初步分析该目标lncRNA可能具有的功能。结果经过基因芯片筛选及分析后,得出两条目标lnCRNA——NR_040090、T065445。经过RT-qPCIR验证可知二者在瘤体中表达均为上调,与基因芯片结果一致。经过lncRNA与mRNA共表达分析以及联合分析可知,NR_040090可能与醛固酮合成相关;T065445则既可参与醛固酮合成,也可能介导肾上腺细胞增生从而形成肿瘤。结论 lncRNA——NR_040090、T065445在醛固酮瘤瘤体中表达上调,前者可能与醛固酮瘤中醛固酮过量合成相关,后者可能与醛固酮合成异常及肿瘤形成相关。
Objective To study the differentially expressed long non-coding RNA(lncRNA) in aldosterone producing adenoma(APA) and analyse the role of lncRNA in the genesis and growth of APA.Methods Using microarray to find out the differentially expressed InRNAs between the tumor and peritumor tissue of APA.After that, to discover the target lncRNAs through analysis and validate their expression levels. Analyzing the functions of target lncRNAs. Results Two IncRN As-NR_040090 and T065445 were selected through the microarray and analysis. They were validated to be up-regulated in the tumor,and the consequences were the same as the microarray-s. From the results of lncRNA and mRNA coexpression and conjoint analysis, we can conclude that NR_040090 may be related to aldosterone synthesis,T065445 may have influence on aldosterone synthesis and adrenocortical cell proliferation which is responsible for tumorgenesis. Conclusion IncRN As-NR_040090 and T065445 were up-regulated in APA tumor, N R_040090 may have relationship with aldosterone synthesis, T065445 may be associated with both aldosterone synthesis and tumorgenesis.
Objective To study the differentially expressed long non-coding RNA(lncRNA) in aldosterone producing adenoma(APA) and analyse the role of lncRNA in the genesis and growth of APA.Methods Using microarray to find out the differentially expressed InRNAs between the tumor and peritumor tissue of APA.After that, to discover the target lncRNAs through analysis and validate their expression levels. Analyzing the functions of target lncRNAs. Results Two IncRN As-NR_040090 and T065445 were selected through the microarray and analysis. They were validated to be up-regulated in the tumor,and the consequences were the same as the microarray-s. From the results of lncRNA and mRNA coexpression and conjoint analysis, we can conclude that NR_040090 may be related to aldosterone synthesis,T065445 may have influence on aldosterone synthesis and adrenocortical cell proliferation which is responsible for tumorgenesis. Conclusion IncRN As-NR_040090 and T065445 were up-regulated in APA tumor, N R_040090 may have relationship with aldosterone synthesis, T065445 may be associated with both aldosterone synthesis and tumorgenesis.
引文
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[13]Konosu-Fukaya S,Nakamura Y,Satoh F,et al.3β-hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma[J].Mol Cell Endocrinol,2015,408:205-212.
[14]Scholl UI,Goh G,St?lting G,et al.Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas andprimary aldosteronism[J].Nat Genet,2013,45(9):1050-1054.
[15]El Ghorayeb N,Bourdeau I,Lacroix A.Role of ACTH and other hormones in the regulation of aldosterone production in primary aldosteronism[J].Front Endocrinol(Lausanne),2016,7:72.
[16]Hattangady NG,Karashima S,Yuan L,et al.Mutated KCNJ5activates the acute and chronic regulatory steps in aldosterone production[J].J Mol Endocrinol,2016,57(1):1-11.
[17]Nanba K,Chen A,Nishimoto K,Rainey WE.Role of Ca2+/calmodulin-dependent protein kinase kinase in adrenal aldosterone production[J].Endocrinology,2015,156(5):1750-1756.
[18]Vouillarmet J,Fernandes-Rosa F,Graeppi-Dulac J,et al.Aldosterone-producing adenoma with a somatic KCNJ5 mutation revealing APC-dependent familial adenomatous polyposis[J].JClin Endocrinol Metab,2016,101(11):3874-3878.
[19]Zennaro MC,Fernandes-Rosa FL,Boulkroun S.Overview of aldosterone-related genetic syndromes and recent advances[J].Curr Opin Endocrinol Diabetes Obes,2018,25(3):147-154.
[2]Akerstrom T,Crona J,Delgado Verdugo A,et al.Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter[J].PLoS One,2012,7(7):e41926.
[3]汪晶彩,王志谦,惠学志,等.原发性醛固酮增多症最新进展[J].世界最新医学信息文摘,2018,(16):63-67.
[4]Prada E T A,Burrello J,Reincke M,et al.Old and new concepts in the molecular pathogenesis of primary aldosteronism[J].Hypertension,2017,70(5):875-881.
[5]Morris KV,Mattick JS.The rise of regulatory RNA[J].Nat Rev Genet,2014,15(6):423-437.
[6]Cech TR,Steitz JA.The noncoding RNA revolution-trashing old rules to forge new ones[J].Cell,2014,157(1):77-94.
[7]Mercer TR,Dinger ME,Mattick JS.Long non-coding RNAs:insights into functions[J].Nat Rev Genet,2009,10(3):155-159.
[8]Ning Q,Li Y,Wang Z,et al.The evolution and expression pattern of human overlapping lncRNA and protein-coding gene pairs[J].Sci Rep,2017,7:42775.
[9]Ransohoff JD,Wei Y,Khavari PA.The functions and unique features of long intergenic non-coding RNA[J].Nat Rev Mol Cell Biol,2017,19(3):143-157.
[10]Wang H,Jiang C.RAB38 confers a poor prognosis,associated with malignant progression and subtype preference in glioma[J].Oncol Rep,2013,30(5):2350-2356.
[11]Hattangady NG,Olala LO,Bollag WB,Rainey WE.Acute and chronic regulation of aldosterone production[J].Mol Cell Endocrinol,2012,350(2):151-162.
[12]Katsumata N,Shinagawa T,Horikawa R,Fujikura K.Novel intronic CYP21A2 mutation in a Japanese patient with classic saltwasting steroid 21-hydroxylase deficiency[J].Metabolism,2010,59(11):1628-1632.
[13]Konosu-Fukaya S,Nakamura Y,Satoh F,et al.3β-hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma[J].Mol Cell Endocrinol,2015,408:205-212.
[14]Scholl UI,Goh G,St?lting G,et al.Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas andprimary aldosteronism[J].Nat Genet,2013,45(9):1050-1054.
[15]El Ghorayeb N,Bourdeau I,Lacroix A.Role of ACTH and other hormones in the regulation of aldosterone production in primary aldosteronism[J].Front Endocrinol(Lausanne),2016,7:72.
[16]Hattangady NG,Karashima S,Yuan L,et al.Mutated KCNJ5activates the acute and chronic regulatory steps in aldosterone production[J].J Mol Endocrinol,2016,57(1):1-11.
[17]Nanba K,Chen A,Nishimoto K,Rainey WE.Role of Ca2+/calmodulin-dependent protein kinase kinase in adrenal aldosterone production[J].Endocrinology,2015,156(5):1750-1756.
[18]Vouillarmet J,Fernandes-Rosa F,Graeppi-Dulac J,et al.Aldosterone-producing adenoma with a somatic KCNJ5 mutation revealing APC-dependent familial adenomatous polyposis[J].JClin Endocrinol Metab,2016,101(11):3874-3878.
[19]Zennaro MC,Fernandes-Rosa FL,Boulkroun S.Overview of aldosterone-related genetic syndromes and recent advances[J].Curr Opin Endocrinol Diabetes Obes,2018,25(3):147-154.