Evidence map›Paper›PMID 40518456›Full record

ArticleJournal of gastroenterology2025

aGenome-scale activation screen reveals lncRNA HNF1A-AS1 promotes pancreatic cancer metastasis through interacting with U2SURP to increase CD44 alternative splicing.

Shan Lei, Zhixue Zhang, Zhirui Zeng, Wenpeng Cao, Yating Sun, Dahuan Li, Jigang Pan, Yingmin Wu, Tuo Zhang, Tengxiang Chen

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In one paragraph

Article in Journal of gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Shan Lei *Department of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Zhixue Zhang *Department of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Zhirui Zeng *Department of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Wenpeng Cao *Department of Anatomy, School of Basic Medicine, Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Yating SunDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Dahuan LiDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Jigang PanDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Yingmin WuDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Tuo ZhangDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Tengxiang ChenDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550009, Guizhou, China. txch@gmc.edu.cn.

Funding

Guizhou Medical University 19NSP034Guizhou Medical University 20NSP020National Natural Science Foundation of China 82103681Science and Technology Program of Guizhou Province No. ZK [2024]159
6 · The paper itself

Abstract

backgroundPancreatic cancer (PC) has a strong ability to invade and metastasize, which has brought insurmountable obstacles to the treatment of PC. Exploring the molecular mechanism of PC metastasis is still the focus of PC research. The purpose of this study was to explore the molecular mechanism of long noncoding RNA HNF1A-AS1 in promoting PC metastasis, hoping to provide help for the diagnosis and treatment of PC.

methodsCRISPR/CRISPR-associated protein 9 (Cas9) single-guide RNA (sgRNA)-pooled lncRNA libraries were used to screen for the critical lncRNAs regulating PC metastasis. Investigation into HNF1A-AS1's impact on PC cell migration and invasion were conducted through both loss-of-function and gain-of-function approaches. A range of techniques, including fluorescence in situ hybridization (FISH), mRNA sequencing, bioinformatics analysis, dual-luciferase reporter assays, RNA pull-down assays, ChIP-PCR, and rescue assay to explore the regulatory mechanism of HNF1A-AS1 in PC metastasis.

resultsSNAI2 activates HNF1A-AS1 transcription. HNF1A-AS1 recruits U2SURP (RRM-dependent domain-dependent) through the 1001-1500 nt region (BR3) to form a functional complex (SNAI2-lncRNA HNF1A-AS1-U2SURP) within the nucleus of PC cells, specifically promoting alternative splicing of CD44 pre-mRNA, transforming it from standard isoform CD44s-CD44v (3-10) isoform, thereby promoting PC invasion and metastasis.

conclusionsThis study revealed for the first time that SNAI2 activates the transcription of HNF1A-AS1, and HNF1A-AS1 promote U2SURP to regulate the alternative splicing of CD44 pre-mRNA, causing it to produce a large number of CD44v (3-10) isoforms, thereby promoting the invasion and metastasis of PC.

Indexed as

Hyaluronan ReceptorsPancreatic NeoplasmsRNA, Long NoncodingAlternative SplicingCell Line, TumorCell MovementGene Expression Regulation, NeoplasticHumansNeoplasm InvasivenessNeoplasm MetastasisCD44 protein, humanHyaluronan Receptorslong non-coding RNA HNF1A-AS1, humanRNA, Long NoncodingHNF1A-AS1MetastasisPancreatic cancerU2SURP

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.