title: Long non-coding RNA ANRIL promotes the invasion and metastasis of thyroid cancer cells through TGF-β/Smad signaling pathway.
abstract: OBJECTIVE
  To investigate the effect of antisense non-coding RNA in the INK4 locus (ANRIL) on invasion and metastasis of thyroid cancer (TC).
  
  
  RESULTS
  ANRIL expression was significantly up-regulated in TC tissues and cells (P < 0.001), and ANRIL expression was significantly different regarding histological grade and LNM (both P < 0.01). The siRNA-mediated ANRIL silencing inhibits proliferation, invasion, and metastasis of TPC-1 and SW579 cells, and lung metastasis, which can be reversed by TGF-β1 siRNA. The mRNA levels of p15INK4b, p14ARF and p16INK4a in TPC-1 and SW579 cells increased significantly after silencing ANRIL (all P < 0.001), and TGF-β1 siRNA could reverse the ANRIL siRNA induced increase of p15INK4b; expressions of TGF-β1 and p-Smad2/3 were increased after silencing ANRIL (both P < 0.05).
  
  
  METHODS
  TC and adjacent normal tissues were collected from 105 TC patients. LncRNA ANRIL expressions were detected by qRT-PCR. The siRNA ANRIL and siRNA TGF-β1 were constructed for TPC-1 and SW579 cell line transfection: si-ANRIL group, si-TGF-β1 group, si-ANRIL + si-TGF-β1 group, negative control group and blank group. Effects of ANRIL silencing on proliferation, invasion and metastasis of TC cells was detected by MTT assay, Transwell assay and tail vein injection of nude mice in vitro and in vivo. TGF-β1 and p-Smad2/3 expressions in TGF-β/Smad signaling pathway were detected by western blot.
  
  
  CONCLUSIONS
  ANRIL may reduce p15INK4B expression through inhibiting TGF-β/Smad signaling pathway, promoting invasion and metastasis of TC cells, and the silencing of ANRIL inhibits the invasion and metastasis of TPC-1 cells.
authors: Department of Breast, Thyroid, and Vascular Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors: Jian-Jie
authors: JJ
authors: Zhao
authors: Department of Breast, Thyroid, and Vascular Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors: Shuai
authors: S
authors: Hao
authors: Department of Breast, Thyroid, and Vascular Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors: Ling-Li
authors: LL
authors: Wang
authors: Department of Breast, Thyroid, and Vascular Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors: Chun-Yan
authors: CY
authors: Hu
authors: Department of Breast, Thyroid, and Vascular Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors: Shu
authors: S
authors: Zhang
authors: Department of Breast, Thyroid, and Vascular Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors: Ling-Ji
authors: LJ
authors: Guo
authors: Department of Breast, Thyroid, and Vascular Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors: Gang
authors: G
authors: Zhang
authors: Department of Breast, Thyroid, and Vascular Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors: Bo
authors: B
authors: Gao
authors: Department of Breast, Thyroid, and Vascular Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors: Yan
authors: Y
authors: Jiang
authors: Department of Breast, Thyroid, and Vascular Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors: Wu-Guo
authors: WG
authors: Tian
authors: Department of Breast, Thyroid, and Vascular Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors: Dong-Lin
authors: DL
authors: Luo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: C561518:CDKN2B antisense RNA, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: TGF-β/Smad signaling pathway; TPC-1; long non-coding RNA ANRIL; p15INK4b; thyroid cancer