Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 22;56(1):72.
doi: 10.1007/s10735-024-10327-w.

LINC02418 suppresses endometrial cancer progression via regulating miR-494-3p/RASGRF1 axis

Hongfeng Li  1 , Jia Bian  1 , Minjie Liu  1 , Yijie Wang  1 , Yapping Shang  1 , Yu Zheng  1 , Xuehe Li  2
Affiliations

LINC02418 suppresses endometrial cancer progression via regulating miR-494-3p/RASGRF1 axis

Hongfeng Li et al. J Mol Histol. .

Abstract

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulatory molecules in cancer biology. Among these, long intergenic non-protein coding RNA 02418 (LINC02418), a recently identified lncRNA, has been linked to endometrial cancer (EC), although its function and operational mechanisms are largely unclear. The present investigation aims to elucidate the molecular mechanism through which LINC02418 influences EC pathogenesis. We employed Western blotting and quantitative real-time PCR to analyze Ras protein specific guanine nucleotide releasing factor 1 (RASGRF1) and LINC02418 expression profiles in EC tissues and cell lines. Functional analyses, including cell proliferation, migration, and invasion assays, were conducted to evaluate the impact of LINC02418 overexpression on EC cells. Xenograft mouse models were established for in vivo validation. The molecular interactions between LINC02418, miR-494-3p, and RASGRF1 were characterized using luciferase reporter and RNA pull-down assays. LINC02418 expression was significantly downregulated in EC tissues and cell lines compared to their normal counterparts. Forced expression of LINC02418 significantly suppressed EC cell proliferation, migration, and invasion in vitro. In xenograft models, LINC02418 overexpression resulted in reduced tumor burden and enhanced cell death. Mechanistically, LINC02418 enhanced RASGRF1 expression by sequestering miR-494-3p, a finding substantiated by RNA pull-down assays. The tumor-suppressive effects of LINC02418 were partially reversed by RASGRF1 silencing and miR-494-3p overexpression. Clinical analyses revealed that reduced RASGRF1 expression correlated with poor histological differentiation, advanced tumor stages, and decreased overall survival in EC patients. Our findings establish LINC02418 as a tumor suppressor that regulates EC progression through modulation of the miR-494-3p/RASGRF1 axis, highlighting its potential as a therapeutic target in EC treatment.

Keywords: Cell migration; Cell proliferation; Endometrial cancer; LINC02418; RASGRF1; miR-494-3p.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflicts of interest: The authors declared that there was no conflicts of interest associated with the manuscript. Ethical approval: The study was approved by the Institutional Review Board at the Affiliated People’s Hospital of Ningbo University following the ethical guidelines of the 1964 Declaration of Helsinki and its amendments. Written informed consent was obtained from all participants or their legal representatives prior to sample collection. Research involving animal participants: The procedures involving animals were approved by the Animal Care and Use Committee at the Affiliated People’s Hospital of Ningbo University, and were meticulously carried out in accordance with the established protocols and statutes governing the management of experimental animals within the institution. Consent for publication: Not applicable.

Similar articles

See all similar articles

References

    1. Anastasiadou E, Jacob LS, Slack FJ (2018) Non-coding RNA networks in cancer. Nat Rev Cancer 18(1):5–18. https://doi.org/10.1038/nrc.2017.99 - DOI - PubMed
    1. Calvo F, Sanz-Moreno V, Agudo-Ibáñez L, Wallberg F, Sahai E, Marshall CJ, Crespo P (2011) RasGRF suppresses Cdc42-mediated tumour cell movement, cytoskeletal dynamics and transformation. Nat Cell Biol 13(7):819–826. https://doi.org/10.1038/ncb2271 - DOI - PubMed
    1. Chen H, Xu Z, Yang B, Zhou X, Kong H (2018) RASGRF1 hypermethylation, a putative biomarker of colorectal cancer. Ann Clin Lab Sci 48(1):3–10 - PubMed
    1. Coan M, Haefliger S, Ounzain S, Johnson R (2024) Targeting and engineering long non-coding RNAs for cancer therapy. Nat Rev Genet. https://doi.org/10.1038/s41576-024-00693-2 - DOI - PubMed
    1. Dedes KJ, Wetterskog D, Ashworth A, Kaye SB, Reis-Filho JS (2011) Emerging therapeutic targets in endometrial cancer. Nat Rev Clin Oncol 8(5):261–271. https://doi.org/10.1038/nrclinonc.2010.216 - DOI - PubMed

MeSH terms

LinkOut - more resources