Dysregulation of the miRNA biogenesis components DICER1, DROSHA, DGCR8 and AGO2 in clear cell renal cell carcinoma in both a Korean cohort and the cancer genome atlas kidney clear cell carcinoma cohort

韩国队列和癌症基因组图谱肾透明细胞癌队列中透明细胞肾细胞癌中 miRNA 生物合成成分 DICER1、DROSHA、DGCR8 和 AGO2 的失调

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作者:Sang Su Lee, Hyeonji Min, Ji Yong Ha, Byung Hoon Kim, Mi Sun Choi, Shin Kim

Abstract

Impairment of microRNA (miRNA) biogenesis may be involved in clear cell renal cell carcinoma (ccRCC). The objective of the present study was to investigate the mRNA levels of important miRNA machinery components, DICER1, DROSHA, DiGeroge syndrome critical region gene 8 (DGCR8), and Argonaute 2 (AGO2), and their correlations with clinicopathological characteristics of ccRCC using mRNA expression data from The Cancer Genome Atlas kidney clear cell carcinoma (TCGA KIRC) cohort and a Korean ccRCC cohort. mRNA levels of DICER1, DROSHA, and DGCR8 were significantly decreased in both cohorts. However, AGO2 was significantly downregulated only in the Korean ccRCC cohort. Additionally, positive correlations were observed between the altered mRNA levels of DICER1 and DROSHA as well as DROSHA and DGCR8 in both cohorts. In the TCGA KIRC cohort, alterations in the mRNA levels of DICER1 were significantly correlated with histological grade. Furthermore, the altered mRNA levels of DGCR8 showed significant associations with sex and histologic grades. However, in the Korean ccRCC cohort, no factors were significantly associated with any clinicopathological parameters, including sex, age, T stage, Fuhrman grade/The International Society of Urological Pathology grade, lymphovascular invasion, and peri-renal fat invasion. Taken together, these findings indicate that DICER1, DROSHA, DGCR8 and AGO2 are significantly dysregulated in ccRCC, suggesting that they are important in the pathophysiology of this malignancy.

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