title: Neuron navigator 2 overexpression indicates poor prognosis of colorectal cancer and promotes invasion through the SSH1L/cofilin-1 pathway.
abstract: BACKGROUND
  Neuron navigator 2 (NAV2) encodes a member of the neuron navigator gene family, which plays a role in tumorigenesis and cell migration. However, the prognostic value of NAV2 expression in colorectal cancer (CRC) patients and the potential pathway through which NAV2 promotes migration and invasion in CRC cell lines is poorly understood.
  
  
  METHODS
  The expression level of NAV2 was detected in CRC tissues from two different CRC cohorts by immunohistochemistry, qRT-PCR and Western blotting; the correlation between NAV2 expression and clinicopathological characters was analyzed, and the prognostic value of NAV2 expression was analyzed using a Cox regression model. CRC cell lines with NAV2 knocked out were used to validate the function and potential pathway used by NAV2 to promote CRC cell migration and invasion.
  
  
  RESULTS
  The results showed that NAV2 was overexpressed in CRC tissues, and it was closely correlated with depth of invasion, and lymph and distant metastasis. Multivariate analysis indicated that high NAV2 expression was a poor prognostic indicator of recurrence-free survival and overall survival in CRC patients. Furthermore, Cox regression analysis revealed that high NAV2 expression integrated with high tumor budding grade was a powerful independent predictive factor of CRC clinical outcome. In vitro and in vivo assays demonstrated that knockdown of NAV2 led to reduced migration and invasion of cancer cells, and the process involved the regulation of F-actin polymerization through the SSH1L/cofilin-1 pathway.
  
  
  CONCLUSIONS
  Based on these findings, NAV2 could serve as both a prognostic biomarker and a potential therapeutic target for patients with NAV2-positive CRC.
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Fengbo
authors.initials: F
authors.lastname: Tan
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Nanhui
authors.initials: N
authors.lastname: Yu
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Pei
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Heli
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Mammary and Thyroid, The First Affiliated Hospital of South China University, Hengyang, China.
authors.forename: Haifan
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Xiangping
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Mammary, The Hunan Cancer Hospital, Changsha, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Emergency, The Hunan Provincial People's Hospital, Changsha, China.
authors.forename: Xingwen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P.R. China. peihaiping1966@hotmail.com.
authors.forename: Haiping
authors.initials: H
authors.lastname: Pei
mesh_terms: D000199:Actins / Q000378:metabolism; D000368:Aged; D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D051338:Cofilin 1 / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D004265:DNA Helicases; D018572:Disease-Free Survival; D005260:Female; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
chemical_list: D000199:Actins; D051338:Cofilin 1; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D010749:Phosphoprotein Phosphatases; C484329:SSH1 protein, human; D004265:DNA Helicases; C465311:NAV2 protein, human