Abstract
Background
Metastasis and chemo-resistance are still important factors that limit the overall efficacy of colorectal cancer treatment. Understanding the detailed molecular mechanism and identifying potential biomarkers are of great value in prognosis prediction and risk stratification.
Objective
We investigated the role of miR-582-5p in colorectal cancer pathogenesis, progression and chemo-resistance. Furthermore, we explored the underlying molecular mechanism of miR-582-5p in modulation of malignant behaviors of colorectal cancer cells.
Methods
Clinical samples and colorectal cancer cell lines were applied to explore miR-582-5p expression level and its significance on tumor cell metastasis and chemo-resistance. Transwell study and cellular survivability study were performed to explore the influences of miR-582-5p expression modulation on tumor cell chemo-resistance and invasion/migration. Dual-luciferase reporter gene assay was conducted to explore the influences of miR-582-5p on its target gene TNKS2.
Results
Colorectal cancer patients with lymph node or distal organ metastatic diseases exhibited significantly lower level of miR-582-5p. In vitro studies have indicated that miR-582-5p inhibition significantly increased migration and chemo-resistant capabilities of tumor cells. And dual-luciferase reporter gene assay demonstrated that miR-582-5p exhibited its influences on the biological behavior of tumor cells by targeting TNKS2.
Conclusions
Our study demonstrated for the first time that miR-582-5p played an important role for colorectal tumor cell metastasis and chemo-resistance. Our research also indicated that miR-582-5p and its target gene TNKS2 could be novel biomarkers for metastatic disease prediction, overall prognosis evaluation, as well as potential therapeutic target for colorectal cancer patients.
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All data generated or analysed during this study are included in this published article.
Abbreviations
- miRNAs:
-
MicroRNAs
- PCR:
-
Polymerase chain reaction
- MOI:
-
Multiplicity of infection
- PVDF:
-
Polyvinylidene difluoride
- LV:
-
Lentiviral vector
- CAFs:
-
Cancer-associated-fibroblasts
- MSI-L:
-
Microsatellite instability-low
- TNKS2:
-
Tankyrase 2
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Conception and design of the research: WX, HZ. Acquisition of data: BC. Analysis and interpretation of data: BS. Statistical analysis: JZ. Drafting the manuscript: WX. Revision of manuscript for important intellectual content: HZ. All authors read and approved the final manuscript.
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Weixing Xiao, Haijun Zhou, Bingrong Chen, Bin Shen and Jun Zhou declare that they have no conflict of interest.
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The study was approved by Ethical Committee of Jiaxing Hospital of Traditional Chinese Medicine Cancer Center. Informed consent was obtained for all patients enrolled in this study.
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13258_2021_1141_MOESM1_ESM.jpg
Supplementary Figure 1 RT-PCR detection of miR-582-5p expression level in normal colon mucosa cell line (FHC) and multiple colorectal cancer cell lines (SW620, HT-29, SW403, KM202L, COLO320DM)
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Xiao, W., Zhou, H., Chen, B. et al. miR-582-5p inhibits migration and chemo-resistant capabilities of colorectal cancer cells by targeting TNKS2. Genes Genom 44, 747–756 (2022). https://doi.org/10.1007/s13258-021-01141-9
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DOI: https://doi.org/10.1007/s13258-021-01141-9