Micro RNA ‐1258 suppresses tumour progression via GRB 2/Ras/Erk pathway in non‐small‐cell lung cancer
Open accessAbstract
Objectives: Lung cancer is still a disease with high morbidity and mortality in the world. Micro RNA s have been proven to act as an indispensable role in the reuse of multiple solid tumours. Although miR‐1258 plays a vital role in suppressing metastasis in breast cancer and gastric cancer, the specific biological function of miR‐1258 in non‐small‐cell lung cancer remains unclear. Methods: The differential expression of miR‐1258 in NSCLC tissues and corresponding paracancerous tissues was detected by qRT ‐ PCR and ISH . Flow cytometry and CCK ‐8, EdU, tubule formation, and senescence assays were performed, and xenograft models were studied to explore the function of miR‐1258. Potential targets of miR‐1258 were verified by dual luciferase reporter assay, qRT ‐ PCR , IHC and Western blotting. Results: In vitro and in vivo gain‐ and loss‐of‐function assays suggested that miR‐1258 inhibits NSCLC cell proliferation and induces senescence and apoptosis. The luciferase reporter assay, IHC and Western blotting analysis showed that GRB 2 is one of the direct targets of miR‐1258. The GRB 2 overexpression plasmid can reverse the functional changes after overexpression of miR‐1258. In contrast, miR‐1258 inhibitor significantly reversed si‐ GRB 2‐induced GRB 2 down‐regulation. Mechanistically, overexpression of miR‐1258 inhibits GRB 2 expression and then leads to inactivation of the Ras/Erk oncogenic pathway. Conclusions: Our results indicate that miR‐1258 can suppress NSCLC progression by targeting the GRB 2/Ras/Erk pathway, which may lead to different insights into potential biomarkers and novel therapeutic strategies for NSCLC patients.
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All three microglial sub-populations showed upregulation of APOE, ATG16L2, BCL2, CCNH and GAS7; negative regulators of senescence GRB2 and NIBAN1 were downregulated with increasing β-amyloid.
“All three microglial sub-populations showed upregulation of APOE, ATG16L2 (an autophagy antagonist gene), BCL2 (encoding a negative regulator of apoptosis), the CDK7 regulator gene CCNH and GAS7 (the growth arrest-specific protein 7 gene). Genes for negative regulators of senescence such as GRB2 and NIBAN1 were downregulated with increasing β-amyloid [17, 21, 34, 55].”
From Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics (2024) · cites this paper as [34]
The Discussion reports that GRB2 upregulation suppressed cellular senescence, supporting its description as a negative regulator of senescence. The paper studies non-small-cell lung cancer cells, however, and does not support the claimed gene-expression changes in microglial sub-populations with increasing β-amyloid. (LLM, conf=0.87)
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- Authors
- Jiang, W., Wei, K., Pan, C., Li, H., Cao, J., Han, X., Tang, Y., Zhu, S., Yuan, W., He, Y., Xia, Y., Chen, L., & Chen, Y.
- Affiliations
- Jiangsu Province Hospital (CN)
- Corresponding author
- Chen, Yijiang
- ORCID
- Venue
- Cell Proliferation
- Publisher
- Wiley
- Published
- 2018-08-02
- Volume
- 51
- Issue
- 6
- Pages
- e12502-e12502
- ISSN
- 0960-7722 (ISSN-L)
- 1365-2184
- PMC
- PMC6528891
- OpenAlex
- W2885409821
- Cited by
- 67
- References
- 35
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 11 · 2021: 9 · 2020: 15 · 2019: 14 · 2018: 3 · 2017: 1
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Proliferation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81572263, 81702262)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- non-small cell lung cancer, Grb2, Ras/ERK pathway, microRNA, tumor progression, apoptosis, cellular senescence, tumour metastasis, therapeutic target
- MeSH terms
- Carcinoma, Non-Small-Cell Lung, Cell Movement, Humans, Lung Neoplasms, Signal Transduction, Down-Regulation, Gene Expression Regulation, Neoplastic, MicroRNAs, Cell Line, Tumor, Cell Proliferation, GRB2 Adaptor Protein
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