The online version of this article (doi:10.1186/s12885-017-3216-6) contains supplementary material, which is available to authorized users.
Shuzhen Chang and Binhe Chen contributed equally to this work.
Tumor metastasis often occurs in hepatocellular carcinoma (HCC) and influences the patient’s prognosis, and microRNAs are reported to play key roles in tumor metastasis. This study was conducted to explore the effect of microRNAs on HCC metastasis.
The levels of miR-181a in HCC tissues, adjacent tissues, metastatic HCC tissues, and non-metastatic HCC tissues at different stages were determined by qRT-PCR. Effect of miR-181a on the proliferation, invasion, and metastasis of HCC cells was estimated by cell counting kits-8 (CCK-8), wound-healing, and Transwell assays. Software analysis and luciferase assays were used to explore the target gene of miR-181a.
MiR-181a was up-regulated in HCC tissues and its expression level in metastatic HCC tissues was much higher than in non-metastasis samples. PTEN was found to be a target gene of miR-181a. MiR-181a had multiple binding sites with the long non-coding RNA (lncRNA) XIST. The regulation of miR-181a on PTEN was mediated by lncRNA XIST. The proliferation and invasion of cells with siXIST were significantly enhanced compared with those of control cells, while knockdown of miR-181a abolished the enhancing effects.
MiR-181a can promote HCC metastasis by targeting PTEN, which is regulated by lncRNA XIST.
Additional file 1: Table S1. Primers used for quantitative real-time PCR. (DOCX 15 kb)12885_2017_3216_MOESM1_ESM.docx
Additional file 2: Table S2. Sequences including the siRNA and the scramble sequence used in transfection assay. (DOCX 15 kb)12885_2017_3216_MOESM2_ESM.docx
Additional file 3: Figure S1. (A) Relative expression of XIST in Huh7 cells after transfection with si-XIST or si-Scramble. ** vs Blank, p < 0.01. (B) Relative expression of XIST in HCCLM3 cells after transfection with pcDNA-XIST or pcDNA-Scramble. ## vs Blank, p < 0.01. (TIFF 164 kb)12885_2017_3216_MOESM3_ESM.tif
Additional file 4: Figure S2. (A) The efficiency of miR-181a inhibitor transfected in HCCLM3 cells was evaluated by qRT-PCR. ** vs inhibitor NC, p < 0.01. (B) The efficiency of miR-181a mimics transfected in Huh7 cells was evaluated by qRT-PCR. ## vs mimics, p < 0.01. (TIFF 118 kb)12885_2017_3216_MOESM4_ESM.tif
Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology (Baltimore, Md). 2011;53(3):1020–2. CrossRef
Hu L, Lau SH, Tzang CH, Wen JM, Wang W, Xie D, Huang M, Wang Y, Wu MC, Huang JF, et al. Association of Vimentin overexpression and hepatocellular carcinoma metastasis. Oncogene. 2004;23(1):298–302. PubMed
van Zijl F, Zulehner G, Petz M, Schneller D, Kornauth C, Hau M, Machat G, Grubinger M, Huber H, Mikulits W. Epithelial-mesenchymal transition in hepatocellular carcinoma. Future oncology (London, England). 2009;5(8):1169–79. CrossRef
Adam L, Zhong M, Choi W, Qi W, Nicoloso M, Arora A, Calin G, Wang H, Siefker-Radtke A, McConkey D, et al. miR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy. Clinical cancer research: an official journal of the American Association for Cancer Research. 2009;15(16):5060–72. CrossRef
Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(9):1485–91. CrossRef
Llovet JM, Bruix J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology (Baltimore, Md). 2008;48(4):1312–27. CrossRef
Budhu A, Jia HL, Forgues M, Liu CG, Goldstein D, Lam A, Zanetti KA, Ye QH, Qin LX, Croce CM, et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology (Baltimore, Md). 2008;47(3):897–907. CrossRef
Zhang X, Nie Y, Du Y, Cao J, Shen B, Li Y. MicroRNA-181a promotes gastric cancer by negatively regulating tumor suppressor KLF6. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine. 2012;33(5):1589–97. CrossRef
Ji J, Yamashita T, Budhu A, Forgues M, Jia HL, Li C, Deng C, Wauthier E, Reid LM, Ye QH, et al. Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology (Baltimore, Md). 2009;50(2):472–80. CrossRef
Zhuo L, Liu J, Wang B, Gao M, Huang A. Differential miRNA expression profiles in hepatocellular carcinoma cells and drug-resistant sublines. Oncol Rep. 2013;29(2):555–62. PubMed
Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology (Baltimore, Md). 2002;36(6):1349–54. CrossRef
Van Tubergen EA, Banerjee R, Liu M, Vander Broek R, Light E, Kuo S, Feinberg SE, Willis AL, Wolf G, Carey T, et al. Inactivation or loss of TTP promotes invasion in head and neck cancer via transcript stabilization and secretion of MMP9, MMP2, and IL-6. Clinical cancer research: an official journal of the American Association for Cancer Research. 2013;19(5):1169–79. CrossRef
Kim D, Kim S, Koh H, Yoon SO, Chung AS, Cho KS, Chung J. Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2001;15(11):1953–62. CrossRef
Engreitz JM, Pandya-Jones A, McDonel P, Shishkin A, Sirokman K, Surka C, Kadri S, Xing J, Goren A, Lander ES, et al. The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science (New York, NY). 2013;341(6147):1237973. CrossRef
- Long non-coding RNA XIST regulates PTEN expression by sponging miR-181a and promotes hepatocellular carcinoma progression
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