Inhibition of microRNA-21 via locked nucleic acid-anti-miR suppressed metastatic features of colorectal cancer cells through modulation of programmed cell death 4
Open accessAbstract
Colorectal cancer is among the most lethal of malignancies, due to its propensity to metastatic spread and multifactorial-chemoresistance. The latter property supports the need to identify novel therapeutic approaches for the treatment of colorectal cancer. MicroRNAs are endogenous non-coding small RNA molecules that function as post-transcriptional regulators of gene expression. Recently, programmed cell death 4 has been identified as a protein that increases during apoptosis. This gene is among the potential targets of miR-21 (OncomiR). Locked nucleic acid–modified oligonucleotides have recently emerged as a potential therapeutic option for targeting microRNAs. The aim of this study was to explore the functional role of locked nucleic acid-anti-miR-21 in the LS174T cell line in vitro and in vivo models. LS174T cells were treated with locked nucleic acid-anti-miR-21 for 24, 48, and 72 h in vitro. The expression of miR-21 and PDCD4 at messenger RNA (mRNA) level was evaluated by quantitative real-time polymerase chain reaction, while the protein level of PDCD4 was determined by Western blotting. Cell migratory behavior and the cluster-forming ability of cells were assessed before and after therapy. The disseminated tumor cells were assessed in the chick chorioallantoic membrane model by Alu quantitative polymerase chain reaction. Locked nucleic acid-anti-miR-21 was transfected successfully into the LS174T cells and inhibited the expression of miR-21. Locked nucleic acid-anti-miR-21 inhibited the migration and the number of cells forming clusters. Moreover, we found that locked nucleic acid-anti-miR-21 transfection was associated with a significant reduction in metastatic properties as assessed by the in ovo model. Our findings demonstrated the novel therapeutic potential of locked nucleic acid-anti-miR-21 in colon adenocarcinoma with high miR-21 expression.
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Nucleotide anti-miR21 drugs inhibit colon cancer cell metastasis by up-regulating PDCD4-protein levels in in vitro experiments.
“nucleotide anti-mir21 drugs inhibit colon cancer cell metastasis up-regulating PDCD4-protein levels in in vitro experiments [100].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [100]
The Results report increased PDCD4 protein after LNA-anti-miR-21 treatment, and the Discussion reports reduced migration and cluster formation in LS174T colorectal cancer cells. The claim overstates the in vitro finding as inhibition of metastasis: the paper assessed metastatic features in cells, while its metastasis-related liver finding came from a chick-egg model, not an in vitro experiment. (LLM, conf=0.86)
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HypoxaMIRs: Key Regulators of Hallmarks of Colorectal Cancer
Coronel-Hernández, J., Delgado-Waldo, I., Cantú de León, D., López-Camarillo, C., Jacobo-Herrera, N., Ramos-Payán, R., & Pérez-Plasencia, C. (2022) · Cells · doi:10.3390/cells11121895 · Cited by 13 · see citing works
- Authors
- Nedaeinia, R., Sharifi, M., Avan, A., Kazemi, M., Nabinejad, A., Ferns, G. A., Ghayour-Mobarhan, M., & Salehi, R.
- Affiliations
- Mashhad University of Medical Sciences (IR)
- Isfahan University of Medical Sciences (IR)
- Isfahan Research Center for Agriculture and Natural Resources, Isfahan, Iran
- Brighton and Sussex Medical School (GB)
- Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Corresponding author
- Salehi, Rasoul
- Venue
- Tumor Biology
- Publisher
- SAGE Publications
- Published
- 2017-03
- Volume
- 39
- Issue
- 3
- Pages
- 101042831769226
- ISSN
- 1010-4283 (ISSN-L)
- 1423-0380
- OpenAlex
- W2600826497
- Cited by
- 47
- References
- 4
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 8 · 2023: 1 · 2022: 7 · 2021: 6 · 2020: 4 · 2019: 9 · 2018: 5 · 2017: 2
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Tumor Biology (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion, cc-by-nc)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by-nc)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- miR-21, PDCD4, colorectal cancer, metastasis, cell migration, cell invasion, chemoresistance, oncogenic microRNA, LS174T cells, chick chorioallantoic membrane model, disseminated tumor cells, microRNA inhibition
- MeSH terms
- Animals, Cell Movement, Chick Embryo, Humans, Liver Neoplasms, Neoplasm Metastasis, Oligonucleotides, Transfection, Colorectal Neoplasms, Genetic Therapy, RNA-Binding Proteins, MicroRNAs, Cell Line, Tumor, Apoptosis Regulatory Proteins
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