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Sökning: id:"swepub:oai:DiVA.org:liu-184683" > Prognostic value an...

Prognostic value and biological function of LRRN4 in colorectal cancer

Xu, Cheng (författare)
Chengdu Univ Tradit Chinese Med, Peoples R China; Hosp Chengdu Univ Tradit Chinese Med, Peoples R China
Chen, Yulin (författare)
Sichuan Univ, Peoples R China
Long, Feiwu (författare)
Sichuan Univ, Peoples R China; Sichuan Univ, Peoples R China; Sichuan Univ, Peoples R China
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Ye, Junman (författare)
Sichuan Univ, Peoples R China
Li, Xue (författare)
Sichuan Univ, Peoples R China
Huang, Qiaorong (författare)
Sichuan Univ, Peoples R China
Yao, Dejiao (författare)
Chengdu Univ Tradit Chinese Med, Peoples R China; Hosp Chengdu Univ Tradit Chinese Med, Peoples R China
Wang, Xiaoli (författare)
Chengdu Univ Tradit Chinese Med, Peoples R China; Southwest Med Univ, Peoples R China
Zhao, Jin (författare)
Sichuan Univ, Peoples R China
Meng, Wentong (författare)
Sichuan Univ, Peoples R China
Mo, Xianming (författare)
Sichuan Univ, Peoples R China
Lu, Ran (författare)
Sichuan Univ, Peoples R China
Fan, Chuanwen (författare)
Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US,Sichuan Univ, Peoples R China; Sichuan Univ, Peoples R China; Sichuan Univ, Peoples R China; Sichuan Univ, Peoples R China
Zhang, Tao (författare)
Chengdu Univ Tradit Chinese Med, Peoples R China; Gen Hosp Western Theater Command, Peoples R China
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 (creator_code:org_t)
2022-04-19
2022
Engelska.
Ingår i: Cancer Cell International. - : BMC. - 1475-2867. ; 22:1
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Colorectal cancer; Neurogenic biomarker; Leucine-rich repeat neuronal 4; Prognosis; RAS; MAPK signal pathways

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