Evidence map›Paper›PMID 39836545›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

A Novel 167-Amino Acid Protein Encoded by CircPCSK6 Inhibits Intrahepatic Cholangiocarcinoma Progression via IKBα Ubiquitination.

Canghai Guan, Jianjun Gao, Xinlei Zou, Wujiang Shi, Yunhe Hao, Yifei Ge, Zhaoqiang Xu, Chengru Yang, Shaowu Bi, Xingming Jiang and 3 more

Abstract read
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In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Canghai GuanGeneral Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.ORCID https://orcid.org/0000-0002-6439-1851
Jianjun GaoGeneral Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.
Xinlei ZouGeneral Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.
Wujiang ShiGeneral Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.
Yunhe HaoGeneral Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.
Yifei GeGeneral Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.
Zhaoqiang XuGeneral Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.
Chengru YangGeneral Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.
Shaowu BiGeneral Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.
Xingming JiangGeneral Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.
Pengcheng KangGeneral Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.
Xiaoxue XuSchool of Health Administration Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.
Xiangyu ZhongGeneral Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin, Heilongjiang Province, 150086, China.

Funding

Heilongjiang Provincial Postdoctoral Science Foundation LBH-Q21023Joint Guidance Project of Heilongjiang Provincial Natural Science Foundation LH2022H018National Natural Science Foundation of China 82270599
6 · The paper itself

Abstract

Intrahepatic cholangiocarcinoma (ICC), a formidable challenge in oncology, demands innovative biomarkers and therapeutic targets. This research highlights the importance of the circular RNA (circRNA) circPCSK6 and its peptide derivative circPCSK6-167aa in ICC. CircPCSK6 is significantly downregulated in both ICC patients and mouse primary ICC models, and its lower expression is linked to adverse prognosis, highlighting its pivotal role in ICC pathogenesis. Functionally, this study elucidates the regulatory effect of circPCSK6-167aa on IκBα ubiquitination within the NF-κB pathway, which is mediated by its competitive binding to the E3 ligase RBBP6. This complex interaction leads to reduced activation of the NF-κB pathway, thereby curbing tumor cell proliferation, migration, invasion, stemness, and hepatic-lung metastasis in vivo. This groundbreaking discovery expands the understanding of circRNA-driven tumorigenesis through atypical signaling pathways. Additionally, this investigation identified EIF4A3 as a detrimental regulator of circPCSK6, exacerbating ICC malignancy. Importantly, by leveraging patient-derived xenograft (PDX), organoids, and organoid-derived PDX models, higher levels of circPCSK6-167aa enhance sensitivity to gemcitabine, indicating its potential to improve the effectiveness of chemotherapy. These insights emphasize the therapeutic promise of targeting circPCSK6-167aa, offering vital biological insights and clinical directions for developing cutting-edge therapeutic approaches, thus revealing innovative strategies and targets for future treatments.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaNF-KappaB Inhibitor alphaRNA, CircularAnimalsCell Line, TumorCell ProliferationDisease ProgressionGene Expression Regulation, NeoplasticHumansMiceSignal TransductionUbiquitinationNF-KappaB Inhibitor alphaRNA, CircularcircCPSK6circular RNAintrahepatic cholangiocarcinomaNF‐κBubiquitination

Identifiers

PMID39836545
PMCPMC11904980

What OpenQuestion holds

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Registered trials

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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.