title: Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/β-catenin signaling pathway.
abstract: BACKGROUND
  Recent studies indicate that long noncoding RNAs (lncRNAs) play a key role in the control of cellular processes such as proliferation, metastasis, and differentiation. The lncRNA dysregulation has been identified in all types of cancer. We previously found that lncRNA AK126698 suppresses cisplatin resistance in A549 cells through the Wnt/β-catenin signaling pathway. However, the clinical significance of lncRNA AK126698 and the molecular mechanisms through which it regulates cancer cell proliferation and migration are largely unknown.
  
  
  METHODS
  We examined the expression of lncRNA AK126698 in 56 non-small cell lung cancer (NSCLC) tissue samples and three NSCLC cell lines using quantitative real-time polymerase chain reaction. Gain and loss of function approaches were used to evaluate the biological function of AK126698 in NSCLC cells. The effects of lncRNA AK126698 on cell proliferation were investigated using cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays, and apoptosis was measured by flow cytometry. Protein levels of AK126698 targets were evaluated by Western blotting.
  
  
  RESULTS
  Our results showed that lncRNA AK126698 was significantly downregulated in NSCLC tissues, compared with paired adjacent nontumor tissue samples. Furthermore, lower AK126698 expression was associated with larger tumor size and advanced tumor stage. Ectopic AK126698 expression inhibited cell proliferation and migration and induced apoptosis. Conversely, decreased AK126698 expression promoted cell proliferation and migration and inhibited cell apoptosis. Importantly, we demonstrated that Frizzled-8, a receptor of Wnt/β-catenin pathway, was a target of AK126698. Furthermore, AK126698 could inhibit the activation of Wnt/β-catenin pathway, which was demonstrated by measuring the expression levels of Axin1, β-catenin, c-myc, cyclin D1, and E-cadherin.
  
  
  CONCLUSIONS
  It was found in the study that lncRNA AK126698 inhibits the proliferation and migration of NSCLC cells by targeting Frizzled-8 to suppress the Wnt/β-catenin signaling pathway. It may provide a new target for therapeutic intervention in NSCLC.
authors.affiliation: Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
keywords: Frizzled-8; NSCLC; Wnt/β-catenin; long noncoding RNAs; migration; proliferation