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长链非编码RNA HNF1A-AS1通过作为竞争性内源性RNA发挥作用,介导miR-34a/SIRT1/p53反馈回路的抑制,从而促进结肠癌的转移进展。

Long non-coding RNA HNF1A-AS1 mediated repression of miR-34a/SIRT1/p53 feedback loop promotes the metastatic progression of colon cancer by functioning as a competing endogenous RNA.

作者信息

Fang Changyi, Qiu Shenglong, Sun Feng, Li Wei, Wang Ziqi, Yue Ben, Wu Xuesong, Yan Dongwang

机构信息

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China.

Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, China.

出版信息

Cancer Lett. 2017 Dec 1;410:50-62. doi: 10.1016/j.canlet.2017.09.012. Epub 2017 Sep 21.


DOI:10.1016/j.canlet.2017.09.012
PMID:28943452
Abstract

In recent years, accumulating evidence indicates that long noncoding RNAs (lncRNAs) have emerged as powerful influence factors in the progression of multiple malignancies. Dysregulation of lncRNA HNF1A-antisense 1 (HNF1A-AS1) has been reported in many types of human cancers, and studies on HNF1A-AS1 function in cancers revealed that HNF1A-AS1could act as either oncogene or tumor suppressor. Nevertheless, the functional involvement of HNF1A-AS1 in colon cancer remains unknown. In this study, we reported that HNF1A-AS1 was frequently upregulated in colon cancer tissues and associated with poor prognosis. Upregulated HNF1A-AS1 promoted colon cancer cell viability, migration and invasion both in vitro and in vivo. HNF1A-AS1 silencing impaired tumor growth and metastasis in xenograft model assay. Moreover, HNF1A-AS1 functioned as an oncogene in metastasis of colon cancer in part through serving as a competing endogenous RNA to modulate miRNA-34a expression, subsequently with repression of miR-34a/SIRT1/p53 feedback loop and activation of canonical Wnt signaling pathway. Our results demonstrated that HNF1A-AS1 mediated the metastatic progression of colon cancer in part through miR-34a/p53 signaling axis, and established its candidacy as a new prognostic biomarker and a potential novel therapeutic target.

摘要

近年来,越来越多的证据表明,长链非编码RNA(lncRNA)已成为多种恶性肿瘤进展中的强大影响因素。在许多类型的人类癌症中都报道了lncRNA HNF1A反义1(HNF1A-AS1)的失调,对HNF1A-AS1在癌症中的功能研究表明,HNF1A-AS1既可以作为癌基因,也可以作为肿瘤抑制因子。然而,HNF1A-AS1在结肠癌中的功能作用仍不清楚。在本研究中,我们报道HNF1A-AS1在结肠癌组织中经常上调,并与不良预后相关。上调的HNF1A-AS1在体外和体内均促进结肠癌细胞的活力、迁移和侵袭。在异种移植模型试验中,HNF1A-AS1沉默会损害肿瘤生长和转移。此外,HNF1A-AS1在结肠癌转移中作为癌基因发挥作用,部分原因是作为竞争性内源性RNA调节miRNA-34a的表达,随后抑制miR-34a/SIRT1/p53反馈环并激活经典Wnt信号通路。我们的结果表明,HNF1A-AS1部分通过miR-34a/p53信号轴介导结肠癌的转移进展,并确立了其作为新的预后生物标志物和潜在新治疗靶点的候选地位。

相似文献

[1]
Long non-coding RNA HNF1A-AS1 mediated repression of miR-34a/SIRT1/p53 feedback loop promotes the metastatic progression of colon cancer by functioning as a competing endogenous RNA.

Cancer Lett. 2017-12-1

[2]
Long non-coding RNA NEAT1 promotes colorectal cancer progression by competitively binding miR-34a with SIRT1 and enhancing the Wnt/β-catenin signaling pathway.

Cancer Lett. 2018-10-9

[3]
LncRNA MNX1-AS1 promotes progression of esophageal squamous cell carcinoma by regulating miR-34a/SIRT1 axis.

Biomed Pharmacother. 2019-6-3

[4]
Long noncoding RNA B3GALT5-AS1 suppresses colon cancer liver metastasis via repressing microRNA-203.

Aging (Albany NY). 2018-12-10

[5]
Long noncoding RNA HNF1A-AS1 indicates a poor prognosis of colorectal cancer and promotes carcinogenesis via activation of the Wnt/β-catenin signaling pathway.

Biomed Pharmacother. 2017-11-6

[6]
LncRNA-HNF1A-AS1 functions as a competing endogenous RNA to activate PI3K/AKT signalling pathway by sponging miR-30b-3p in gastric cancer.

Br J Cancer. 2020-6

[7]
EGR1-Mediated Transcription of lncRNA-HNF1A-AS1 Promotes Cell-Cycle Progression in Gastric Cancer.

Cancer Res. 2018-9-5

[8]
The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma.

Oncotarget. 2015-4-20

[9]
lncRNA HNF1A-AS1 modulates non-small cell lung cancer progression by targeting miR-149-5p/Cdk6.

J Cell Biochem. 2019-6-26

[10]
Silencing UNC5B antisense lncRNA 1 represses growth and metastasis of human Colon cancer cells via raising miR-622.

Artif Cells Nanomed Biotechnol. 2020-12

引用本文的文献

[1]
The role of SIRT1 in the development of gastrointestinal tumors.

Front Cell Dev Biol. 2025-6-11

[2]
Identification of a PANoptosis-related long noncoding rna risk signature for prognosis and immunology in colon adenocarcinoma.

BMC Cancer. 2025-4-10

[3]
Long non‑coding RNAs as diagnostic and prognostic biomarkers for colorectal cancer (Review).

Oncol Lett. 2024-8-8

[4]
The functions and mechanisms of long non-coding RNA in colorectal cancer.

Front Oncol. 2024-7-4

[5]
MicroRNA-34 and gastrointestinal cancers: a player with big functions.

Cancer Cell Int. 2024-5-9

[6]
Identification and Functional Characterization of Alternative Transcripts of LncRNA HNF1A-AS1 and Their Impacts on Cell Growth, Differentiation, Liver Diseases, and in Response to Drug Induction.

Noncoding RNA. 2024-4-21

[7]
LINC00482 sponged miR-2467-3p to promote bone metastasis of prostate cancer through activating Wnt/β-catenin signaling pathway.

J Bone Oncol. 2023-7-21

[8]
The effect of a traditional Chinese quadri-combination therapy and its component quercetin on recurrent spontaneous abortion: A clinical trial, network pharmacology and experiments-based study.

Front Pharmacol. 2022-10-19

[9]
mA Modification of Long Non-Coding RNA HNF1A-AS1 Facilitates Cell Cycle Progression in Colorectal Cancer via IGF2BP2-Mediated CCND1 mRNA Stabilization.

Cells. 2022-9-27

[10]
LncRNA-AC009948.5 promotes invasion and metastasis of lung adenocarcinoma by binding to miR-186-5p.

Front Oncol. 2022-8-19

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