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长链非编码 RNA LINC00460 通过 miR-342-3p 依赖的 AGR2 上调促进肝细胞癌的肿瘤生长和转移。

Long noncoding RNA LINC00460 conduces to tumor growth and metastasis of hepatocellular carcinoma through miR-342-3p-dependent AGR2 up-regulation.

机构信息

Department of Hepato-Pancreato-Biliary Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China.

Department of Special Treatment I and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.

出版信息

Aging (Albany NY). 2020 Jun 3;12(11):10544-10555. doi: 10.18632/aging.103278.

DOI:10.18632/aging.103278
PMID:32493835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7346032/
Abstract

Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor in the world. It ranks third among cancer-induced deaths worldwide and has the characteristics of high metastasis and high recurrence rate. Long non-coding RNA (LncRNA) LINC00460 is significantly up-regulated in multiple types of cancers and is closely related to the progression of tumors. However, effects of LINC00460 and corresponding regulatory path in HCC are still poorly investigated.In our study, we found that expression of LINC00460 was up-regulated in HCC tissues and cell lines compared with the control. Then we revealed that knockdown of LINC00460 suppressed cell proliferation and cell mobility and induced cell apoptosis in HCC cells. Further study demonstrated that knockdown of LINC00460 suppressed the progression of HCC by elevating the expression of microRNA (miRNA, miR)-342-3p. Besides that, metastasis marker, Anterior gradient homolog 2 (AGR2) was found to be a target of miR-342-3p and overexpression of AGR2 promoted the progression of HCC. Finally, the experiments further verified the anti-tumor effects of LINC00460 / miR-342-3p / AGR2 axis in HCC.The LINC00460 / miR-342-3p / AGR2 axis exerts anti-tumor effect in HCC and , consolidating and expanding the research about targeted gene therapy for early diagnosis and treatment of HCC.

摘要

肝细胞癌 (HCC) 是世界上第五种最常见的恶性肿瘤。它在全球癌症死亡原因中排名第三,具有高转移和高复发率的特点。长链非编码 RNA (LncRNA) LINC00460 在多种类型的癌症中显著上调,与肿瘤的进展密切相关。然而,LINC00460 及其在 HCC 中的相应调节途径的作用仍未得到充分研究。在我们的研究中,我们发现与对照相比,LINC00460 在 HCC 组织和细胞系中的表达上调。然后我们揭示了敲低 LINC00460 抑制 HCC 细胞的增殖和迁移,并诱导细胞凋亡。进一步的研究表明,敲低 LINC00460 通过上调 microRNA (miRNA,miR)-342-3p 的表达来抑制 HCC 的进展。此外,转移标志物,前梯度同源物 2 (AGR2) 被发现是 miR-342-3p 的靶标,AGR2 的过表达促进了 HCC 的进展。最后,实验进一步验证了 LINC00460/miR-342-3p/AGR2 轴在 HCC 中的抗肿瘤作用。LINC00460/miR-342-3p/AGR2 轴在 HCC 中发挥抗肿瘤作用,巩固和扩展了针对 HCC 的早期诊断和治疗的靶向基因治疗研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/ff3780e0f4d0/aging-12-103278-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/30c56a48a8bb/aging-12-103278-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/7dc36123ae90/aging-12-103278-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/da1970c1405b/aging-12-103278-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/d4b09c528c3c/aging-12-103278-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/f62a118becfb/aging-12-103278-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/ff3780e0f4d0/aging-12-103278-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/30c56a48a8bb/aging-12-103278-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/7dc36123ae90/aging-12-103278-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/da1970c1405b/aging-12-103278-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/d4b09c528c3c/aging-12-103278-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/f62a118becfb/aging-12-103278-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d5/7346032/ff3780e0f4d0/aging-12-103278-g006.jpg

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本文引用的文献

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Downregulation of long noncoding RNA LINC00460 expression suppresses tumor growth in vitro and in vivo in gastric cancer.长链非编码 RNA LINC00460 表达下调抑制胃癌的体内外肿瘤生长。
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