HBx‑associated long non‑coding RNA activated by TGF‑β promotes cell invasion and migration by inducing autophagy in primary liver cancer

Zhang,Yuheng; Li,Jun; Wang,Shuai; Yang,Faji; Zhou,Yuan; Liu,Yang; Zhu,Wei; Shi,Xiaolei

doi:10.3892/ijo.2019.4908

HBx‑associated long non‑coding RNA activated by TGF‑β promotes cell invasion and migration by inducing autophagy in primary liver cancer

Authors:
- Yuheng Zhang
- Jun Li
- Shuai Wang
- Faji Yang
- Yuan Zhou
- Yang Liu
- Wei Zhu
- Xiaolei Shi
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Affiliations: Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Anesthesiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China
Published online on: November 4, 2019 https://doi.org/10.3892/ijo.2019.4908
Pages: 337-347

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Abstract

Hepatitis B virus (HBV) x protein (HBx) has been reported as the primary pathogenic factor involved in HBV‑related liver cancer; however, the mechanisms underlying how HBx promotes tumor‑associated invasion and metastasis remain unclear. Long noncoding RNA activated by transforming growth factor (TGF)‑β (lncRNA‑ATB) is a novel oncogenic lncRNA stimulated by TGF‑β, which is closely associated with the invasion and metastasis of liver cancer. In the present study, whether lncRNA‑ATB was involved in HBx‑mediated hepatocarcinogenesis was investigated. The expression of lncRNA‑ATB in 26 primary liver cancer tissues and lentivirus transfected HBx‑HepG2 cell lines was detected, and it was revealed that more advanced tumor‑node‑metastasis staging and increased expression of lncRNA‑ATB in liver cancer tissues were significantly associated with HBV infection. It was further demonstrated that the expression levels of lncRNA‑ATB and TGF‑β were elevated in HepG2 cells following HBx‑vector transfection, which was accompanied with increased autophagy. Conversely, knockdown of lncRNA‑ATB or TGF‑β could suppress this effect. Furthermore, such suppression on autophagy in HepG2 cells could be alleviated by the induction of starvation. In addition, the invasive and migration abilities of HBx‑HepG2 cells were increased compared with HepG2 cells, while knockdown of lncRNA‑ATB or TGF‑β could reduce these abilities. In conclusion, the results of the present study revealed that HBx was closely associated with oncogenic lncRNA‑ATB. HBx‑induced autophagy could upregulate the expression of TGF‑β and lncRNA‑ATB. This may be considered to be a potential mechanism underlying HBV‑induced hepatocarcinogenesis.

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