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Cancer Cell International
Published in: Cancer Cell International 1/2022

Open Access 01-12-2022 | Colorectal Cancer | Primary research

Prognostic value and biological function of LRRN4 in colorectal cancer

Authors: Cheng Xu, Yulin Chen, Feiwu Long, Junman Ye, Xue Li, Qiaorong Huang, Dejiao Yao, Xiaoli Wang, Jin Zhao, Wentong Meng, Xianming Mo, Ran Lu, Chuanwen Fan, Tao Zhang

Published in: Cancer Cell International | Issue 1/2022

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Abstract

Background

Several 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.

Methods

We 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.

Results

We 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.

Conclusions

Our 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.
Appendix
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Metadata
Title
Prognostic value and biological function of LRRN4 in colorectal cancer
Authors
Cheng Xu
Yulin Chen
Feiwu Long
Junman Ye
Xue Li
Qiaorong Huang
Dejiao Yao
Xiaoli Wang
Jin Zhao
Wentong Meng
Xianming Mo
Ran Lu
Chuanwen Fan
Tao Zhang
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-022-02579-x

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