Downregulation of lncRNA APCDD1L-AS1 due to DNA hypermethylation and loss of VHL protein expression promotes the progression of clear cell renal cell carcinoma.
Downregulation of lncRNA APCDD1L-AS1 due to DNA hypermethylation and loss of VHL protein expression promotes the progression of clear cell renal cell carcinoma.
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DOI：
10.7150/ijbs.71519
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发表时间：
2022
影响因子：
9.2
通讯作者：
Gong K
中科院分区：
文献类型：
--
作者：
Yang W;Zhou J;Zhang Z;Zhang K;Xu Y;Li L;Cai L;Gong Y;Gong K
背景：目前的研究仅表明长链非编码RNA（lncRNA）APCDD1L-AS1作为一种新型lncRNA，可能在口腔鳞状细胞癌和肺癌中发挥作用。然而，其在透明细胞肾细胞癌（ccRCC）中的潜在作用及其可能的作用机制仍不清楚。方法：利用临床标本的TCGA-KIRC和GEO数据以及qRT-PCR和焦磷酸测序结果来鉴定APCDD1L-AS1的表达水平和DNA甲基化状态。通过功能实验确定APCDD1L-AS1过表达对ccRCC生长和转移的影响。利用Western blot和串联质量标签（TMT）探讨APCDD1L-AS1与VHL表达之间的关系及其下游机制。结果：APCDD1L-AS1在ccRCC中表达下调。 APCDD1L-AS1 表达降低与较高的肿瘤分期和组织学分级以及较短的 RFS（无复发生存期）有关。此外，APCDD1L-AS1过表达抑制了ccRCC细胞的体外和体内生长和转移。此外，DNA 高甲基化和 von Hippel Lindau (VHL) 蛋白表达缺失可能导致 APCDD1L-AS1 表达减少。此外，APCDD1L-AS1过表达引起的组蛋白表达失调可能是抑制ccRCC进展的重要机制之一。结论：APCDD1L-AS1能够抑制ccRCC的进展，其表达下降可能是由于DNA高甲基化和VHL蛋白表达缺失所致。因此，APCDD1L-AS1可能作为ccRCC治疗的新靶点。
Background: The current studies only indicated that long non-coding RNA (lncRNA) APCDD1L-AS1, as a novel lncRNA, may play a role in oral squamous cell carcinoma and lung cancer. However, its potential role in clear cell renal cell carcinoma (ccRCC) and its possible mechanism of action remain vague. Methods: TCGA-KIRC and GEO data and qRT-PCR and pyrosequencing results of clinical specimens were used to identify the expression level and DNA methylation status of APCDD1L-AS1. The effects of APCDD1L-AS1 overexpression on ccRCC growth and metastasis were determined by function experiments. Western blot and Tandem mass tags (TMT) were utilized to explore the relationship between APCDD1L-AS1 and VHL expression and its downstream underlying mechanisms. Results: The expression of APCDD1L-AS1 was downregulated in ccRCC. Decreased APCDD1L-AS1 expression was related to higher tumor stage and histological grade and shorter RFS (Relapse-free survival). Besides, APCDD1L-AS1 overexpression restrained the growth and metastasis of ccRCC cells in vitro and in vivo. Moreover, reduced APCDD1L-AS1 expression could be caused by DNA hypermethylation and loss of von Hippel Lindau (VHL) protein expression. Furthermore, the dysregulation of histones expression caused by APCDD1L-AS1 overexpression may be one of the important mechanisms to suppress the progression of ccRCC. Conclusion: APCDD1L-AS1 was able to inhibit the progression of ccRCC, and its decreased expression could be caused by DNA hypermethylation and loss of VHL protein expression. Therefore, APCDD1L-AS1 may serve as a new therapeutic target in the treatment of ccRCC.
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影响因子：
9
作者：
Chen T;Liu R;Niu Y;Mo H;Wang H;Lu Y;Wang L;Sun L;Wang Y;Tu K;Liu Q
通讯作者：
Liu Q
影响因子：
4.9
作者：
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通讯作者：
Wu D
影响因子：
11.2
作者：
Chen, Haobin;Yan, Yan;Costa, Max
通讯作者：
Costa, Max
影响因子：
64.8
作者：
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通讯作者：
Ratcliffe, PJ
影响因子：
5.2
作者：
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通讯作者：
Tucci M