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长链非编码RNA ASAP1-IT1通过调控miR-1294/TGFBR1通路促进肝细胞癌进展。

LncASAP1-IT1 promotes hepatocellular carcinoma progression through the regulation of the miR-1294/TGFBR1 pathway and .

作者信息

Qin Xiaohui, Wang Shunxiang

机构信息

Department of Hepatobiliary Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Department of General Surgery, Handan First Hospital, Handan, China.

出版信息

J Gastrointest Oncol. 2023 Jun 30;14(3):1451-1461. doi: 10.21037/jgo-23-327. Epub 2023 Jun 19.

DOI:10.21037/jgo-23-327
PMID:37435227
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10331754/
Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is the most common tumor with severe morbidity and high mortality. The lncRNA ASAP1-IT1 [the intronic transcript 1 (IT-1) of ArfGAP with SH3 domain, ankyrin repeat and PH domain 1 (ASAP1)] have been shown to promote tumor formation in a variety of cancers. This study sought to investigate the effects of dysregulated ASAP1-IT1 on the biological processes of HCC.

METHODS

The expression levels of ASAP1-IT1 in 30 paired HCC and adjacent non-tumor tissues were measured by real-time-quantitative polymerase chain reaction (RT-qPCR). Several functional tests were performed to investigate the molecular mechanism of ASAP1-IT1 in HCC progression.

RESULTS

Our study showed that ASAP1-IT1 was highly expressed in the HCC tissues and cell lines. The knockdown of ASAP1-IT1 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) progression and enhanced the sorafenib sensitivity of the HCC cells. Further investigations revealed that ASAP1-IT1 served as a sponge of microRNA-1294 (miR-1294) to promote transforming growth factor beta receptor 1 (TGFBR1) expression. In addition, the tumor-promoting effect of ASAP1-IT1 was blocked by inhibiting miR-1294/TGFBR1. Tumorigenic assays in nude mice demonstrated that the inhibition of ASAP1-IT1 inhibited the growth of HCC .

CONCLUSIONS

These results suggest that lncASAP1-IT1 promotes HCC development by targeting TGFBR1 through miR-1294, which provides a potential target for HCC diagnosis and treatment.

摘要

背景

肝细胞癌（HCC）是最常见的肿瘤，发病率高且死亡率高。长链非编码RNA ASAP1-IT1[含SH3结构域、锚蛋白重复序列和PH结构域的ArfGAP 1（ASAP1）的内含子转录本1（IT-1）]已被证明在多种癌症中促进肿瘤形成。本研究旨在探讨ASAP1-IT1失调对HCC生物学过程的影响。

方法

采用实时定量聚合酶链反应（RT-qPCR）检测30对HCC及癌旁非肿瘤组织中ASAP1-IT1的表达水平。进行了多项功能测试以研究ASAP1-IT1在HCC进展中的分子机制。

结果

我们的研究表明，ASAP1-IT1在HCC组织和细胞系中高表达。敲低ASAP1-IT1可抑制细胞增殖、迁移、侵袭和上皮-间质转化（EMT）进程，并增强HCC细胞对索拉非尼的敏感性。进一步研究表明，ASAP1-IT1作为微小RNA-1294（miR-1294）的海绵，促进转化生长因子β受体1（TGFBR1）的表达。此外，抑制miR-1294/TGFBR1可阻断ASAP1-IT1的促肿瘤作用。裸鼠致瘤试验表明，抑制ASAP1-IT1可抑制HCC的生长。

结论

这些结果表明，lncASAP1-IT1通过miR-1294靶向TGFBR1促进HCC发展，这为HCC的诊断和治疗提供了一个潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/4a0c3c275158/jgo-14-03-1451-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/9ad034151997/jgo-14-03-1451-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/373b5f4ba406/jgo-14-03-1451-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/832fdb3bc7ab/jgo-14-03-1451-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/26ec20a9fb62/jgo-14-03-1451-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/b504e232259b/jgo-14-03-1451-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/4a0c3c275158/jgo-14-03-1451-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/9ad034151997/jgo-14-03-1451-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/373b5f4ba406/jgo-14-03-1451-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/832fdb3bc7ab/jgo-14-03-1451-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/26ec20a9fb62/jgo-14-03-1451-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/b504e232259b/jgo-14-03-1451-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5846/10331754/4a0c3c275158/jgo-14-03-1451-f6.jpg

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