ArticleCancer cell international2022
Prognostic value and biological function of LRRN4 in colorectal cancer.
Article in Cancer cell international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 5 citations in OpenAlex.
- Establishment of a novel mouse model of colorectal cancer by orthotopic transplantation.BMC cancer · 2025Article
- Leucine-rich repeat neuronal 1 as a prognostic indicator and functional modulator in breast cancer.Frontiers in oncology · 2025Article
- Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer.Biomolecules & biomedicine · 2024Article
- Role of LRRN4 in promoting malignant behavior in a p53- and Rb-defective human fallopian tube epithelial cell line.American journal of cancer research · 2023Article
- Network pharmacology and molecular docking to elucidate the mechanism of pulsatilla decoction in the treatment of colon cancer.Frontiers in pharmacology · 2022Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
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Abstract
backgroundSeveral nervous and nerve-related biomarkers have been detected in colorectal cancer (CRC) and can contribute to the progression of CRC. However, the role of leucine-rich repeat neuronal 4 (LRRN4), a recently identified neurogenic marker, in CRC remains unclear.
methodsWe examined the expression and clinical outcomes of LRRN4 in CRC from TCGA-COREAD mRNA-sequencing datasets and immunohistochemistry in a Chinese cohort. Furthermore, colony formation, flow cytometry, wound healing assays and mouse xenograft models were used to investigate the biological significance of LRRN4 in CRC cell lines with LRRN4 knockdown or overexpression in vitro and in vivo. In addition, weighted coexpression network analysis, DAVID and western blot analysis were used to explore the potential molecular mechanism.
resultsWe provide the first evidence that LRRN4 expression, at both the mRNA and protein levels, was remarkably high in CRC compared to controls and positively correlated with the clinical outcome of CRC patients. Specifically, LRRN4 was an independent prognostic factor for progression-free survival and overall survival in CRC patients. Further functional experiments showed that LRRN4 promoted cell proliferation, cell DNA synthesis and cell migration and inhibited apoptosis. Knockdown of LRRN4 can correspondingly decrease these effects in vitro and can significantly suppress the growth of xenografts. Several biological functions and signaling pathways were regulated by LRRN4, including proteoglycans in cancer, glutamatergic synapse, Ras, MAPK and PI3K. LRRN4 knockdown resulted in downregulation of Akt, p-Akt, ERK1/2 and p-ERK1/2, the downstream of the Ras/MAPK signaling pathway, overexpression of LRRN4 leaded to the upregulation of these proteins.
conclusionsOur results suggest that LRRN4 could be a biological and molecular determinant to stratify CRC patients into distinct risk categories, and mechanistically, this is likely attributable to LRRN4 regulating several malignant phenotypes of neoplastic cells via RAS/MAPK signal pathways.
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