Evidence map›Paper›PMID 31208913›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019

Hypoxia Induces Drug Resistance in Colorectal Cancer through the HIF-1α/miR-338-5p/IL-6 Feedback Loop.

Ke Xu, Yueping Zhan, Zeting Yuan, Yanyan Qiu, Haijing Wang, Guohua Fan, Jie Wang, Wei Li, Yijun Cao, Xian Shen and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing 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

98 citing papers in PubMed.

  1. Review
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  8. Nutritional indicators as predictive and prognosis biomarkers for neoadjuvant chemoradiotherapy outcomes in patients with locally advanced rectal cancer.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025
    Article
  9. Review
  10. Review
  11. Article
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  13. Use of Radiomics in Characterizing Tumor Hypoxia.International journal of molecular sciences · 2025
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025
    Review
  20. HIF-1 and HIF-2 in cancer: structure, regulation, and therapeutic prospects.Cellular and molecular life sciences : CMLS · 2025
    Review

38 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

13 authors.

Ke XuInterventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China; Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China; Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, Hefei 230032, China. Electronic address: kexu2577@shutcm.edu.cn.
Yueping ZhanCentral Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Zeting YuanInterventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China; Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, Hefei 230032, China.
Yanyan QiuInterventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Haijing WangInterventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Guohua FanInterventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Jie WangDepartment of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Wei LiDepartment of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Yijun CaoDepartment of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Xian ShenThe Second Affiliated Hospital of Wenzhou Medical University, Zhejiang 325035, China.
Jun ZhangDivision of Hematology, Oncology and Blood & Marrow Transplantation, Department of Internal Medicine, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Xin LiangState Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China. Electronic address: xin.liang@ecust.edu.cn.
Peihao YinInterventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China; Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China; Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, Hefei 230032, China. Electronic address: yinpeihao@shutcm.edu.cn.

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Christopher K Laubenthal · 2000 to 2026
$70.0M
6 · The paper itself

Abstract

Hypoxia is associated with poor prognosis and therapeutic resistance in cancer patients. Accumulating evidence has shown that microRNA (miRNA) plays an important role in the acquired drug resistance in colorectal carcinoma (CRC). However, the role of miRNA in hypoxia-induced CRC drug resistance remains to be elucidated. Here, we identified a hypoxia-triggered feedback loop that involves hypoxia-inducible transcription factor 1α (HIF-1α)-mediated repression of miR-338-5p and confers drug resistance in CRC. In this study, the unbiased miRNA array screening revealed that miR-338-5p is downregulated in both hypoxic CRC cell lines tested. Repression of miR-338-5p was required for hypoxia-induced CRC drug resistance. Furthermore, we identified interleukin-6 (IL-6), which mediates STAT3/Bcl2 activation under hypoxic conditions, as a direct miR-338-5p target. The resulting HIF-1α/miR-338-5p/IL-6 feedback loop was necessary for drug resistance in colon cancer cell lines. Using CRC patient samples, we found miR-338-5p has a negative correlation with HIF-1α and IL-6. Finally, in a xenograft model, overexpressing miR-338-5p in CRC cells and HIF-1α inhibitor PX-478 were able to enhance the sensitivity of CRC to oxaliplatin (OXA) via suppressing the HIF-1α/miR-338-5p/IL-6 feedback loop in vivo. Taken together, our results uncovered an HIF-1α/miR-338-5p/IL-6 feedback circuit that is critical in hypoxia-mediated drug resistance in CRC; targeting each member of this feedback loop could potentially reverse hypoxia-induced drug resistance in CRC.

Indexed as

Drug Resistance, NeoplasmAnimalsCell Line, TumorCell ProliferationCell SurvivalColorectal NeoplasmsFeedback, PhysiologicalGene Expression Regulation, NeoplasticHCT116 CellsHumansHypoxia-Inducible Factor 1, alpha SubunitInterleukin-6MiceMicroRNAsNeoplasm TransplantationOxaliplatinHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitIL6 protein, humanInterleukin-6MicroRNAsMIRN338 microRNA, humanOxaliplatincolorectal cancerdrug resistanceHIF-1αIL-6miR-338-5p

Identifiers

PMID31208913
PMCPMC6822233

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.