Evidence map›Paper›PMID 36691031›Full record

ArticleMolecular cancer2023

A novel polypeptide encoded by the circular RNA ZKSCAN1 suppresses HCC via degradation of mTOR.

Runjie Song, Shuoqian Ma, Jiajia Xu, Xin Ren, Peilan Guo, Huijiao Liu, Peng Li, Fan Yin, Mei Liu, Qiang Wang and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 1 pooled it
23.9field-weighted citation impact, top 1% of its field
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

89 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.

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  5. Acta pharmaceutica Sinica. B · 2026
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29 more citing papers are in PubMed but not listed here.

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

17 authors at 7 institutions in 3 countries.

Runjie Song *State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Shuoqian Ma *State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Jiajia Xu *State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Xin Ren *State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Peilan GuoState Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Huijiao LiuState Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Peng LiState Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Fan YinDepartment of Oncology, The Second Medical Centre & National Clinical Research Center of Geriatric Disease, Chinese PLA General Hospital, Beijing, 100071, China.
Mei LiuDepartment of Pathology, Chinese PLA General Hospital, Beijing, 100071, China.
Qiang WangDepartment of Urology, Peking University People's Hospital, Beijing, 100044, China.
Lei YuDepartment of Thoracic Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
Jiali LiuState Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Binwei DuanDepartment of General Surgery CenterBeijing You An Hospital, Clinical Center for Liver Cancer, Capital Medical University, Beijing, China.
Nafis A RahmanDepartment of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
Sławomir WołczyńskiDepartment of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Bialystok, Poland.
Guangming LiDepartment of General Surgery CenterBeijing You An Hospital, Clinical Center for Liver Cancer, Capital Medical University, Beijing, China.
Xiangdong LiState Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. xiangdongli68@126.com.
China Agricultural University · CNCapital Medical University · CNChinese PLA General Hospital · CNMedical University of Białystok · PLBeijing YouAn Hospital · CNPeking University People's Hospital · CNUniversity of Turku · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundhsa_circ_0001727 (circZKSCAN1) has been reported to be a tumor-associated circRNA by sponging microRNAs. Intriguingly, we found that circZKSCAN1 encoded a secretory peptide (circZKSaa) in the liver. The present study aims to elucidate the potential role and molecular mechanism of circZKSaa in the regulation of hepatocellular carcinoma (HCC) progression.

methodsThe circRNA profiling datasets (RNA-seq data GSE143233 and GSE140202) were reanalyzed and circZKSCAN1 was selected for further study. Mass spectrometry, polysome fractionation assay, dual-luciferase reporter, and a series of experiments showed that circZKSCAN1 encodes circZKSaa. Cell proliferation, apoptosis, and tumorigenesis in nude mice were examined to investigate the functions of circZKSaa. Mechanistically, the relationship between the circZKSaa and mTOR in HCC was verified by immunoprecipitation analyses, mass spectrometry, and immunofluorescence staining analyses.

resultsReceiver operating characteristic (ROC) analysis demonstrated that the secretory peptide circZKSaa encoded by circZKSCAN1 might be the potential biomarker for HCC tissues. Through a series of experiments, we found that circZKSaa inhibited HCC progression and sensitize HCC cells to sorafenib. Mechanistically, we found that the sponge function of circZKSCAN1 to microRNA is weak in HCC, while overexpression of circZKSaa promoted the interaction of FBXW7 with the mammalian target of rapamycin (mTOR) to promote the ubiquitination of mTOR, thereby inhibiting the PI3K/AKT/mTOR pathway. Furthermore, we found that the high expression of cicZKSCAN1 in sorafenib-treated HCC cells was regulated by QKI-5.

conclusionsThese results reveal that a novel circZKSCAN1-encoded peptide acts as a tumor suppressor on PI3K/AKT/mTOR pathway, and sensitizes HCC cells to sorafenib via ubiquitination of mTOR. These findings demonstrated that circZKSaa has the potential to serve as a therapeutic target and biomarker for HCC treatment.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsMicroRNAsAnimalsCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansMammalsMiceMice, NudePeptidesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRNA, CircularSirolimusMicroRNAsPeptidesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRNA, CircularSirolimusSorafenibTOR Serine-Threonine KinasesBiomarkercircZKSaaHCCmTORSorafenib

Identifiers

PMID36691031
PMCPMC9869513
OpenAlexW4317739614

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.