Evidence map›Paper›PMID 31695022›Full record

ArticleCell death & disease2019

miR-223 overexpression inhibits doxorubicin-induced autophagy by targeting FOXO3a and reverses chemoresistance in hepatocellular carcinoma cells.

Yue Zhou, Enjiang Chen, Yuexiao Tang, Jiayan Mao, Jian Shen, Xiaoxiao Zheng, Shangzhi Xie, Shufen Zhang, Ying Wu, Hao Liu and 6 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

76 citing papers in PubMed, 105 citations in OpenAlex.

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16 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

16 authors at 5 institutions in 2 countries.

Yue ZhouDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, 310009, Hangzhou, Zhejiang, China.
Enjiang ChenThe Second Affiliated Hospital of Zhejiang University, School of Medicine, 310009, Hangzhou, Zhejiang, China.
Yuexiao TangDepartment of Genetics, Research Center for Molecular Medicine, Institute of Cell Biology, Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University School of Medicine, 310058, Hangzhou, Zhejiang, China.
Jiayan MaoCancer Institute of Integrated traditional Chinese and Western Medicine, Key laboratory of cancer prevention and therapy combining traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, 310012, Hangzhou, Zhejiang, China.
Jian ShenCancer Institute of Integrated traditional Chinese and Western Medicine, Key laboratory of cancer prevention and therapy combining traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, 310012, Hangzhou, Zhejiang, China.
Xiaoxiao ZhengCancer Institute of Integrated traditional Chinese and Western Medicine, Key laboratory of cancer prevention and therapy combining traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, 310012, Hangzhou, Zhejiang, China.
Shangzhi XieCancer Institute of Integrated traditional Chinese and Western Medicine, Key laboratory of cancer prevention and therapy combining traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, 310012, Hangzhou, Zhejiang, China.
Shufen ZhangCancer Institute of Integrated traditional Chinese and Western Medicine, Key laboratory of cancer prevention and therapy combining traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, 310012, Hangzhou, Zhejiang, China.
Ying WuCancer Institute of Integrated traditional Chinese and Western Medicine, Key laboratory of cancer prevention and therapy combining traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, 310012, Hangzhou, Zhejiang, China.
Hao LiuDepartment of Surgery, Anschutz Medical Campus, University of Colorado, Aurora, CO, 80045, USA.
Xiao ZhiDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, 310009, Hangzhou, Zhejiang, China.
Tao MaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, 310009, Hangzhou, Zhejiang, China.
Haibin NiDepartment of Gastrointestinal Surgery, Tongde Hospital of Zhejiang Province, 310012, Hangzhou, Zhejiang, China.
Jiabin ChenDepartment of Medical Oncology, Tongde Hospital of Zhejiang Province, 310012, Hangzhou, Zhejiang, China.
Kequn ChaiCancer Institute of Integrated traditional Chinese and Western Medicine, Key laboratory of cancer prevention and therapy combining traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, 310012, Hangzhou, Zhejiang, China. ckq3301@aliyun.com.
Wei ChenCancer Institute of Integrated traditional Chinese and Western Medicine, Key laboratory of cancer prevention and therapy combining traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, 310012, Hangzhou, Zhejiang, China. wei_chen@zju.edu.cn.
Tongde Hospital of Zhejiang Province · CNFirst Affiliated Hospital Zhejiang University · CNSecond Affiliated Hospital of Zhejiang University · CNUniversity of Colorado Anschutz Medical Campus · USZhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Doxorubicin is conventionally used in chemotherapy against hepatocellular carcinoma (HCC), but acquired resistance developed during long-term therapy limits its benefits. Autophagy, a conserved catabolic process for cellular self-protection and adaptation to the changing environment, is regarded as a potential clinical target to overcome doxorubicin resistance. In this study, the potential role of miR-223 in modulating doxorubicin-induced autophagy and sensitivity were evaluated in four transfected human HCC cell lines, and the in vivo relevance was assessed using a mouse xenograft model of HCC. We found that the well-defined miR-223 is expressed at low levels in doxorubicin treated HCC cells and that miR-223 overexpression inhibits the doxorubicin-induced autophagy that contributes to chemoresistance. Blockade of autophagic flux by chloroquine resulted in the failure of miR-223 inhibitor to suppress doxorubicin sensitivity of HCC cells. We further identified FOXO3a as a direct downstream target of miR-223 and primary mediator of the regulatory effect of miR-223 on doxorubicin-induced autophagy and chemoresistance in HCC cells. Finally, we confirmed the enhancement of doxorubicin sensitivity by agomiR-223 in xenograft models of HCC. These findings establish a novel miRNA-based approach for autophagy interference to reverse doxorubicin resistance in future chemotherapy regimens against human HCC.

Indexed as

AnimalsApoptosisAutophagyCarcinoma, HepatocellularCell ProliferationDoxorubicinForkhead Box Protein O3Gene Expression Regulation, NeoplasticHep G2 CellsHumansLiver NeoplasmsMiceMicroRNAsXenograft Model Antitumor AssaysDoxorubicinForkhead Box Protein O3FOXO3 protein, humanMicroRNAsMIR223, human

Identifiers

PMID31695022
PMCPMC6834650
OpenAlexW2988921614

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.