SP1 induced long non-coding RNA AGAP2-AS1 promotes cholangiocarcinoma proliferation via silencing of CDKN1A.

SP1 induced long non-coding RNA AGAP2-AS1 promotes cholangiocarcinoma proliferation via silencing of CDKN1A.
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DOI:
10.1186/s10020-020-00222-x
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发表时间:
2021-02-01
期刊:
Molecular medicine (Cambridge, Mass.)
影响因子:
--
通讯作者:
Wang K
Wang K
中科院分区:
其他
文献类型:
--
作者:
Ji H;Wang J;Lu B;Li J;Zhou J;Wang L;Xu S;Peng P;Hu X;Wang K

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LncRNA可以在多个水平上对基因进行调控,如表观遗传学、选择性剪接和对mRNA降解的调控。然而,lncRNA在胆管细胞癌中的作用机制尚不清楚。这一点值得进一步探讨。我们研究了AGAP2-AS1在32例CCA组织和两个CCA细胞系中的表达。我们在CCA中发现了一个由SP1诱导的lncRNA AGAP2-AS1,并用基因敲除和过表达的方法研究了AGAP2-AS1在体外的生物学作用。芯片和RIP验证了AGAP2-AS1的可能靶点。在CCA肿瘤组织中,AGAP2-AS1表达显著上调。SP1诱导的AGAP2-AS1在肿瘤发生中起重要作用。AGAP2-AS1基因敲除可显著抑制CCA细胞的增殖和诱导细胞凋亡。此外,我们还证实了AGAP2-AS1能促进CCA的增殖。结论:长非编码RNA AGAP2-AS1对胆管癌细胞的增殖有促进作用。
LncRNA can regulate gene at various levels such as apparent genetics, alternative splicing, and regulation of mRNA degradation. However, the molecular mechanism of LncRNA in cholangiocarcinoma is still unclear. This deserves further exploration. We investigated the expression of AGAP2-AS1 in 32 CCA tissues and two CCA cell lines. We found a LncRNA AGAP2-AS1 which induced by SP1 has not been reported in CCA, and Knockdown and overexpression were used to investigate the biological role of AGAP2-AS1 in vitro. CHIP and RIP were performed to verify the putative targets of AGAP2-AS1. AGAP2-AS1 was significantly upregulated in CCA tumor tissues. SP1 induced AGAP2-AS1 plays an important role in tumorigenesis. AGAP2-AS1 knockdown significantly inhibited proliferation and caused apoptosis in CCA cells. In addition, we demonstrated that AGAP2-AS1 promotes the proliferation of CCA. We conclude that the long non-coding RNA AGAP2-AS1 plays a role in promoting the proliferation of cholangiocarcinoma.
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