Evidence map›Paper›PMID 41639725›Full record

ArticleJournal of experimental & clinical cancer research : CR2026

KNTC1 initiates a KNTC1/E2F8/MYC positive feedback loop to facilitate tumorigenesis and enhance chemoresistance in bladder cancer.

Kailai Chen, Hecheng Su, Feng Pei, Xi Chen, Meiqi Xu, Fang Chai, Yakun Luo

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In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Kailai Chen *NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150001, China.
Hecheng Su *NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150001, China.
Feng Pei *NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150001, China.
Xi ChenNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150001, China.
Meiqi XuNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150001, China.
Fang ChaiKey Laboratory for Photochemical Biomaterials and Energy Storage Materials of Heilongjiang Province, Key Laboratory for Photonic and Electronic Bandgap Materials of Ministry of Education, College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin, 150025, China. fangchai@gmail.com.
Yakun LuoNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150001, China. luoyankun@hrbmu.edu.cn.

Funding

National Natural Science Foundation of China 82503606Natural Science Foundation of Heilongjiang Province YQ2023H015Research Fund of the Fourth Affiliated Hospital of Harbin Medical University HYDSYRCYJ02
6 · The paper itself

Abstract

backgroundBladder cancer (BLCA) is a lethal malignancy frequently challenged by chemoresistance and limited therapeutic options. Kinetochore-associated 1 (KNTC1) has been implicated in cancer, yet its precise role, regulatory mechanism, and therapeutic potential in BLCA remain largely unexplored.

methodsWe analyzed KNTC1 expression and its clinical relevance using public databases (TCGA, GEO) and clinical specimens. Functional roles of KNTC1 in proliferation, invasion, metastasis, and gemcitabine resistance were assessed through in vitro and in vivo experiments (CCK-8, transwell, xenograft models). Mechanistic insights were gained via RNA-seq, co-immunoprecipitation, chromatin immunoprecipitation (ChIP), and luciferase reporter assays. A poly (ß-amino ester) (PAE)-based nanoparticle was synthesized for targeted in vivo delivery of KNTC1 siRNA.

resultsKNTC1 was significantly upregulated in BLCA tissues, and its high expression correlated with poor patient prognosis. Functionally, KNTC1 promoted BLCA cell proliferation, invasion, metastasis, and gemcitabine resistance. Mechanistically, KNTC1 bound to the transcription factor E2F8 and facilitated its nuclear translocation, thereby enhancing E2F8-mediated transcriptional activation of MYC. MYC, in turn, transcriptionally upregulated KNTC1, forming a positive feedback loop that drove hyperactivation of the oncogenic PI3K/AKT/mTOR pathway. Silencing KNTC1, especially in combination with a MYC inhibitor (10058-F4), overcame gemcitabine resistance in vitro and in vivo. Therapeutic delivery of KNTC1 siRNA via a novel PAE nanocarrier (PAE@shKNTC1) significantly suppressed lung metastasis in a preclinical model.

conclusionOur study identifies a novel KNTC1/E2F8/MYC positive feedback axis that drives BLCA tumorigenesis and chemoresistance. KNTC1 serves as both a prognostic biomarker and a promising therapeutic target, with targeted inhibition offering a potential novel strategy for BLCA treatment.

Indexed as

Drug Resistance, NeoplasmProto-Oncogene Proteins c-mycUrinary Bladder NeoplasmsAnimalsCarcinogenesisCell Line, TumorCell ProliferationDeoxycytidineFeedback, PhysiologicalFemaleGemcitabineGene Expression Regulation, NeoplasticHumansMiceMice, NudeXenograft Model Antitumor AssaysDeoxycytidineGemcitabineMYC protein, humanProto-Oncogene Proteins c-mycBladder cancerE2F8Gemcitabine resistanceKNTC1MYCPI3K/AKT/mTOR

Identifiers

PMID41639725
PMCPMC12879452

What Socratic 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 Socratic graph.