Evidence map›Paper›PMID 33423358›Full record

ArticleCancer science2021

KHDRBS3 promotes multi-drug resistance and anchorage-independent growth in colorectal cancer.

Shoichi Ukai, Naoya Sakamoto, Daiki Taniyama, Kenji Harada, Ririno Honma, Ryota Maruyama, Kazuhito Naka, Takao Hinoi, Yuji Takakura, Wataru Shimizu and 2 more

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

Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

12 citing papers in PubMed, 29 citations in OpenAlex.

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  12. RestoringFrontiers in oncology · 2021
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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

12 authors at 2 institutions in 1 country.

Shoichi UkaiDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID https://orcid.org/0000-0001-8491-1183
Naoya SakamotoDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID https://orcid.org/0000-0001-6273-0189
Daiki TaniyamaDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Kenji HaradaDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID https://orcid.org/0000-0002-8995-2846
Ririno HonmaDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Ryota MaruyamaDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Kazuhito NakaDepartment of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Takao HinoiDepartment of Clinical and Molecular Genetics, Hiroshima University Hospital, Hiroshima, Japan.
Yuji TakakuraDepartment of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Wataru ShimizuDepartment of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Hideki OhdanDepartment of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Wataru YasuiDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID https://orcid.org/0000-0002-8647-8405
Hiroshima University · JPHiroshima University Hospital · JP

Funding

Japan Society for the Promotion of Science JP18J11110Japan Society for the Promotion of Science JP18K07017Japan Society for the Promotion of Science JP19H03443
6 · The paper itself

Abstract

5-Fluorouracil (5-FU) is one of the most frequently used pharmacological agents in the treatment of colorectal cancer (CRC). Resistance to chemotherapy is a major cause of treatment failure of CRC, and it is a well known fact that cancer stem cells play a significant role in the acquisition of drug resistance. In this study, we focused on the KHDRBS3 gene that encodes KH RNA Binding Domain Containing, Signal Transduction Associated 3. We first clarified the relationship between KHDRBS3 and 5-FU resistance. We then observed higher expression levels of KHDRBS3 in KRAS-mutant organoids and cell lines in comparison with KRAS wild-type organoids and cell lines. Immunohistochemical analysis using CRC cases revealed that the prognosis of KHDRBS3-positive patients was significantly worse compared with that of KHDRBS3-negative patients. Univariate and multivariate Cox proportional hazards analyses showed that KHDRBS3 was an independent prognostic factor in patients with CRC. We determined that KHDRBS3 might play a crucial role in the acquisition of stem cell properties, such as drug resistance and spheroid/organoid formation, by regulating CD44 variant expression and the Wnt signaling pathway. In an immunodeficient mouse model, KHDRBS3-positive cells showed efficient tumor formation and formed metastatic lesions in the lungs. These results indicated that KHDRBS3 plays a crucial role in drug resistance and anchorage-independent growth by maintaining stem cell-like features in CRC cells. KHDRBS3 could be a promising candidate marker for predicting chemotherapeutic effect and prognosis in CRC patients.

Indexed as

AgedAged, 80 and overAnimalsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorColectomyColonColorectal NeoplasmsDrug Resistance, MultipleDrug Resistance, NeoplasmFemaleFluorouracilGene Expression Regulation, NeoplasticGene Knockout TechniquesHumansHyaluronan ReceptorsCD44 protein, humanFluorouracilHyaluronan ReceptorsKHDRBS3 protein, humanKRAS protein, humanProto-Oncogene Proteins p21(ras)RNA-Binding Proteins5-FUcancer stem cellcolorectal cancerdrug resistanceKHDRBS3

Identifiers

PMID33423358
PMCPMC7935809
OpenAlexW3119907188

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.