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Long non-coding RNA ANRIL promotes the invasion and metastasis of thyroid cancer cells through TGF-β/Smad signaling pathway

Jian-Jie Zhao, Shuai Hao, Ling-Li Wang, Chun-Yan Hu, Shu Zhang, Ling-Ji Guo, Gang Zhang, Bo Gao, Yan Jiang, Wu-Guo Tian and Dong-Lin Luo _

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Oncotarget. 2016; 7:57903-57918. https://doi.org/10.18632/oncotarget.11087

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Jian-Jie Zhao1, Shuai Hao1, Ling-Li Wang1, Chun-Yan Hu1, Shu Zhang1, Ling-Ji Guo1, Gang Zhang1, Bo Gao1, Yan Jiang1, Wu-Guo Tian1, Dong-Lin Luo1

1Department of Breast, Thyroid, and Vascular Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China

Correspondence to:

Dong-Lin Luo, email: [email protected]

Keywords: long non-coding RNA ANRIL, thyroid cancer, p15INK4b, TGF-β/Smad signaling pathway, TPC-1

Received: March 11, 2016     Accepted: July 09, 2016     Published: August 05, 2016


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).

Materials and 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.

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