title: Overexpression of Long Non-Coding RNA ZXF2 Promotes Lung Adenocarcinoma Progression Through c-Myc Pathway.
abstract: OBJECTIVE
  To investigate the expression of long non-coding RNA ZXF2 in lung adenocarcinoma tissues and its effect on cell proliferation, migration and invasion.
  
  
  METHODS
  Forty pairs of cancerous and adjacent non-cancerous lung adenocarcinoma specimens were collected for the studies. Quantitative real-time PCR was used to analyze the expression of ZXF2 in tumor tissues and adjacent normal tissues. The expression of ZXF2 was correlated with patients' clinico-pathological data. Molecular pathway controlled by ZXF2 was explored by using small interfering RNA (siRNA) technology. CCK-8 cell proliferation assay, flow cytometry analysis and transwell assays were used to evaluate cell proliferation, migration and invasion.
  
  
  RESULTS
  The expression of ZXF2 was 2 fold or higher in 27 out of 40 (67.5%) cases of lung adenocarcinoma specimens than that in non-cancerous tissues (P<0.05). The relative expression level of ZXF2 was positively correlated with tumor lymph node metastasis (χ(2)=8.485, P<0.05) and poor prognosis of the patients (p=0.0217). In order to explore the molecular mechanisms of ZXF2 mediated tumor progression, ZXF2 expression was inhibited by siRNA in A549 cells, a highly aggressive and metastatic lung adenocarcinoma cell line. We found that siRNA-ZXF2 treatment inhibited cell proliferation (P<0.01) leading to cell cycle arrest (P<0.01). The cell migration and invasion were suppressed by siRNA-ZXF2 treatment (P<0.01). Further biochemical studies revealed that the knockdown of ZXF2 led to down regulation of c-Myc signaling.
  
  
  CONCLUSIONS
  ZXF2 was overexpressed in lung adenocarcinoma tissues and the high expression of ZXF was closely related to tumor progression through c-Myc related pathway. Given the fact that both ZXF2 and c-Myc are located in the same chromosome 8q24.2 loci, the potential interaction between ZXF2 and c-Myc might be a novel target for treatment of lung adenocarcinoma.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, P.R.China.
authors.forename: Ze-Tian
authors.initials: ZT
authors.lastname: Yang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.forename: Xian-Guo
authors.initials: XG
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Tan
authors.forename: Frank
authors.initials: F
authors.lastname: Yi
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Zhao
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering