Evidence map›Paper›PMID 40466438›Full record

ArticleClinics (Sao Paulo, Brazil)2025

CircHIPK3's dual role in promoting angiogenesis and inhibiting apoptosis through FASN mRNA stabilization in gallbladder cancer.

ZhenWei Li, HaiJiu Wang, Cheng Wang, ZhiXin Wang, Zhi Xie, JinMing Liu

Abstract read
In one paragraph

Article in Clinics (Sao Paulo, Brazil), 2025. 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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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

ZhenWei LiDepartment of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, Xining City, Qinghai Province, China; Qinghai Provincial Key Laboratory of Hydatid Disease Research, Xining City, Qinghai Province, China.
HaiJiu WangDepartment of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, Xining City, Qinghai Province, China.
Cheng WangDepartment of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, Xining City, Qinghai Province, China.
ZhiXin WangDepartment of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, Xining City, Qinghai Province, China.
Zhi XieDepartment of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, Xining City, Qinghai Province, China; Qinghai Provincial Key Laboratory of Hydatid Disease Research, Xining City, Qinghai Province, China. Electronic address: xie7835zhi@hotmail.com.
JinMing LiuDepartment of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, Xining City, Qinghai Province, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo investigate the mechanism by which circHIPK3 enhances FASN stability by inhibiting the ubiquitinated degradation of ALYREF on Gallbladder Cancer (GBC).

methodsRT-qPCR was performed to detect circHIPK3 in GBC tissues and to analyze the relationship between circHIPK3 and clinicopathological characteristics of GBC patients. CCK-8 and colony formation assays were performed to study the proliferation of GBC cells, flow cytometry to detect apoptosis, tube formation assay to test angiogenesis, and Transwell assay to study migration and invasion. A nude mice implantation assay was conducted. CircHIPK3, FASN and SKP2 were assessed using RT-qPCR and western blot. Ubiquitination assay was performed to detect ALYREF ubiquitination, and RNA pull-down and RIP to investigate the binding relationship between circHIPK3, ALYREF and FASN.

resultsCircHIPK3 was upregulated in GBC tissues, with elevated expression correlating with TNM stages and lymph node metastasis. CircHIPK3 knockdown suppressed GBC progression by inhibiting proliferation, angiogenesis, migratory and invasive capacity while promoting apoptosis in vitro, paralleled by reduced tumor growth in vivo. CircHIPK3 stabilized ALYREF via inhibiting ubiquitination-mediated degradation. ALYREF knockdown phenocopied the tumor-suppressive effects of circHIPK3 depletion, whereas ALYREF overexpression rescued circHIPK3 knockdown-induced suppression of malignant phenotypes. CircHIPK3 stabilizes FASN mRNA through ALYREF. Overexpressing FASN counteracted the actions of circHIPK3 downregulation on cellular angiogenesis and apoptosis.

conclusionCircHIPK3 enhances FASN stability by inhibiting ALYREF ubiquitination degradation, promoting angiogenesis, and inhibiting apoptosis in GBC. This study positions circHIPK3 as a promising prognostic biomarker and therapeutic target in GBC, with ALYREF and FASN emerging as critical mechanistic nodes within this oncogenic pathway.

Indexed as

ApoptosisFatty Acid Synthase, Type IGallbladder NeoplasmsNeovascularization, PathologicRNA, CircularRNA StabilityAngiogenesisAnimalsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMice, NudeFASN protein, humanFatty Acid Synthase, Type IRNA, CircularRNA, MessengerALYREFCircHIPK3FASNGallbladder cancerUbiquitination

Identifiers

PMID40466438
PMCPMC12171766

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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.