Evidence map›Paper›PMID 39917927›Full record

ArticleCurrent radiopharmaceuticals2025

Role of the p53/miR-34a/SIRT1 Feedback Loop in Metformin-induced Radiosensitivity of Colorectal Cancer Cells.

Ensiyeh Bahadoran, Yazdan Zafari, Ali Homaei, Manijeh Jalilvand, Sahar Moghbelinejad

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Article in Current radiopharmaceuticals, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

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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

5 citing papers in PubMed.

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4 · The record

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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

5 authors.

Ensiyeh BahadoranSchool of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.ORCID 0000-0001-8299-1466
Yazdan ZafariDepartment of Hematology and Medical Oncology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.ORCID 0000-0001-7207-7902
Ali HomaeiSurgery Department, Harvard Medical School, Boston, USA.
Manijeh JalilvandCellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran.
Sahar MoghbelinejadCellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran.ORCID 0000-0002-7653-8689

Funding

Cellular and Molecular Research Center of the Qazvin University of Medical Science 83411
6 · The paper itself

Abstract

introductionMetformin induces radiation sensitivity in cancer cells, including colorectal cancer cells; however, the exact molecular mechanisms underlying its radiosensitive effects are not yet known. In this study, we investigated the role of the p53/miR-34a/SIRT1 pathway in the radiosensitivity of colon cancer cells.

methodsThe study was carried out from 2020 to 2022 at the Qazvin University of Medical Science's Cellular and Molecular Research Center. Two colorectal cancer cell lines (SW480 and SW620) obtained from primary and secondary tumors derived from a single patient were used as the study samples. After subjecting the cells to 50 Gy of radiation, we generated radioresistant cell lines. Resistant cells were treated with 50 μM metformin. Metformin-treated and untreated resistant cells constituted the study groups. The expression levels of miR-34-a and Sirtunin1 (SIRT1) were evaluated using Quantitative Real-time PCR. The rates of cell proliferation and apoptosis were assessed using a Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Western blot analysis was performed to quantify the expression of proteins. For statistical analysis, the Student's ttest was carried out to examine the mean differences between the two groups, and analysis of variance (ANOVA) was used to examine additional groups.

resultsOur results showed that the expression of miR-34-a was downregulated (0.29 ± 0.11) in radiation-resistant cancer cells (P <0.001), while the expression of SIRT-1 was upregulated (4.5 ± 0.25) (P <0.001). Metformin increased the radiosensitivity of colon cancer cells in a time- and dose-dependent manner. Treatment with 50 μM metformin after 48h caused decreased cell viability and increased apoptosis in resistant cells. We observed downregulation of SIRT-1 (1.1 ± 0.45) and upregulation of miR-34-a (4.3 ± 1.3) (P <0.001) in metformin-treated cells. In contrast, western blotting results showed the upregulation of acetylated P53 in metformin-treated cells. Metformin function was reversed by SIRT1 inhibitors or by transfection with miR-34-a overexpressing plasmids.

conclusionBased on these results, one of the radiosensitivity mechanisms of metformin in colorectal cancer is the modulation of the p53/miR-34a/SIRT1 loop.

Indexed as

Colorectal NeoplasmsMetforminMicroRNAsRadiation-Sensitizing AgentsRadiation ToleranceSirtuin 1Tumor Suppressor Protein p53ApoptosisCell Line, TumorCell ProliferationFeedback, PhysiologicalGene Expression Regulation, NeoplasticHumansMetforminMicroRNAsMIRN34 microRNA, humanRadiation-Sensitizing AgentsSIRT1 protein, humanSirtuin 1TP53 protein, humanTumor Suppressor Protein p53apoptosis.cell proliferationColorectal cancermetforminmicroRNAsp53 pathwayradiosensitizationsirtuin 1

Identifiers

PMID39917927

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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.