title: DC - SIGNR by influencing the lncRNA HNRNPKP2 upregulates the expression of CXCR4 in gastric cancer liver metastasis.
abstract: Profiling evidences of selectin demonstrate that they play an crucial role in cancer progression and metastasis. However, DC-SIGNR as a family member of selectin participates in gastric cancer liver metastasis remains unknown.
  
  
  
  The serum level of DC-SIGNR was evaluated in gastric cancer patients by ELISA. Manipulation DC-SIGNR expression in BGC823 and SGC7901 cell lines was mediated by lentivirus. Investigation the biological effects of DC-SIGNR were verified by MTT, wounding and transwell in vitro and experiments on animals to confirm gastric cancer liver metastasis by IVIS. Insights of the mechanism were employed microarray and bioinformatic analysis. Further to confirm the results were conducted by qRT-PCR, western blot and by flow cytometry.
  
  
  
  DC-SIGNR serum level was significantly increased in gastric cancer patients compared with healthy group. Additionally, DC-SIGNR level was associated with an advanced pathological stage in gastric cancer patients. DC-SIGNR knockdown inhibited the proliferation, migration and invasion of gastric cancer cells in vitro and suppressed the liver metastasis in vivo. While, DC-SIGNR overexpression promoted cell proliferation, migration and invasion. In mechanism, HNRNPKP2 as a lncRNA was upregulated after DC-SIGNR knockdown. Importantly, STAT5A promoted HNRNPKP2 expression after knockdown DC-SIGNR. Furthermore after HNRNPKP2 depletion, the downstream target gene CXCR4 was downregulated.
  
  
  
  DC-SIGNR promoted gastric cancer liver metastasis mediated with HNRNPKP2 which expression was regulated by STAT5A. And HNRNPKP2 decreased the expression of downstream target gene CXCR4. These findings indicated potential therapeutic candidates for gastric cancer liver metastasis.
authors.affiliation: Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, lvshun South Road West 9, Dalian, 116044, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Shahekou District Zhongshan Road no. 467, 116023, Dalian, China.
authors.forename: Qianshi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Shahekou District Zhongshan Road no. 467, 116023, Dalian, China.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Shahekou District Zhongshan Road no. 467, 116023, Dalian, China.
authors.forename: Menglang
authors.initials: M
authors.lastname: Yuan
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, lvshun South Road West 9, Dalian, 116044, China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, lvshun South Road West 9, Dalian, 116044, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, lvshun South Road West 9, Dalian, 116044, China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, lvshun South Road West 9, Dalian, 116044, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.affiliation: Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, lvshun South Road West 9, Dalian, 116044, China.
authors.forename: Heya
authors.initials: H
authors.lastname: Na
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Shahekou District Zhongshan Road no. 467, 116023, Dalian, China. rsydl@aliyun.com.
authors.forename: Shuangyi
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, lvshun South Road West 9, Dalian, 116044, China. zyf04112002@aliyun.com.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Zuo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D037181:Lectins, C-Type / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D062085:RNA, Long Noncoding / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C433029:CLEC4M protein, human; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D062085:RNA, Long Noncoding; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; D050799:STAT5 Transcription Factor
keywords: CXCR4; DC-SIGNR; Gastric cancer; Liver metastasis; STAT5A; lncRNA HNRNPKP2