Modulation of miR‑122 expression affects the interferon response in human hepatoma cells

Li,Aimei; Qian,Jun; He,Junming; Zhang,Qingmeng; Zhai,Aixia; Song,Wuqi; Li,Yujun; Ling,Hong; Zhong,Zhaohua; Zhang,Fengmin

doi:10.3892/mmr.2012.1233

February 2013 Volume 7 Issue 2

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February 2013 Volume 7 Issue 2

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Article

Modulation of miR‑122 expression affects the interferon response in human hepatoma cells

Authors:
- Aimei Li
- Jun Qian
- Junming He
- Qingmeng Zhang
- Aixia Zhai
- Wuqi Song
- Yujun Li
- Hong Ling
- Zhaohua Zhong
- Fengmin Zhang
View Affiliations / Copyright

Affiliations: Department of Microbiology, Harbin Medical University, Ministry of Education of China, Harbin 150081, P.R. China, Heilongjiang Key Laboratory of Immunity and Infection, Harbin Medical University, Ministry of Education of China, Harbin 150081, P.R. China, Bio‑pharmaceutical Key Laboratory, Harbin Medical University, Ministry of Education of China, Harbin 150081, P.R. China
Pages: 585-590
|
Published online on: December 14, 2012

https://doi.org/10.3892/mmr.2012.1233
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Abstract

Type I interferon (IFN) is believed to play significant roles in limiting tumor growth. It has been revealed that the induction of endogenous IFN expression is one of the key mechanisms for successful IFN therapy. However, recent studies have shown that the efficacy of type I IFN therapy has limitations in the clinical treatment of certain tumors, including hepatocellular carcinoma (HCC). It has been revealed that the expression of miR‑122 is significantly decreased in HCC and that restoration of miR‑122 expression may improve the prognosis of this condition. Previous studies also showed that patients with low miR‑122 levels in the liver responded poorly to the IFN therapy. We previously identified that the IFN expression was reduced when miR‑122 was suppressed in human oligodendrocytes. Based on these studies, it was hypothesized that the expression of miR‑122 may modulate the endogenous IFN expression and subsequently affect the treatment outcome of IFN therapy for HCC. The results of the present study showed that miR‑122‑abundant Huh7 cells responded more significantly than miR‑122‑deficient HepG2 cells when treated with exogenous IFN. Upregulation of miR‑122 significantly increased the ability of exogenous IFN‑induced IFN expression, while downregulation of miR‑122 decreased this ability. These data indicate that a high level of miR‑122 expression may promote the expression of type I IFN induced by exogenous IFNs and further contribute to IFN therapy for HCC.

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1	Motola-Kuba D, Zamora-Valdes D, Uribe M and Mendez-Sanchez N: Hepatocellular carcinoma. An overview. Ann Hepatol. 5:16–24. 2006.
2	Okuda K: Primary liver cancers in Japan. Cancer. 45:2663–2669. 1980. View Article : Google Scholar
3	Stark GR, Kerr IM, Williams BR, Silverman RH and Schreiber RD: How cells respond to interferons. Annu Rev Biochem. 67:227–264. 1998. View Article : Google Scholar : PubMed/NCBI
4	Haller O, Kochs G and Weber F: The interferon response circuit: induction and suppression by pathogenic viruses. Virology. 344:119–130. 2006. View Article : Google Scholar : PubMed/NCBI
5	Deonarain R, Verma A, Porter AC, Gewert DR, Platanias LC and Fish EN: Critical roles for IFN-beta in lymphoid development, myelopoiesis, and tumor development: links to tumor necrosis factor alpha. Proc Natl Acad Sci USA. 100:13453–13458. 2003. View Article : Google Scholar : PubMed/NCBI
6	Gresser I and Belardelli F: Endogenous type I interferons as a defense against tumors. Cytokine Growth Factor Rev. 13:111–118. 2002. View Article : Google Scholar : PubMed/NCBI
7	Dunn GP, Bruce AT, Sheehan KC, et al: A critical function for type I interferons in cancer immunoediting. Nat Immunol. 6:722–729. 2005. View Article : Google Scholar : PubMed/NCBI
8	Wang L, Tang ZY, Qin LX, et al: High-dose and long-term therapy with interferon-alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential. Hepatology. 32:43–48. 2000. View Article : Google Scholar
9	Yano H, Ogasawara S, Momosaki S, et al: Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells in vitro and in vivo. Liver Int. 26:964–975. 2006. View Article : Google Scholar : PubMed/NCBI
10	Lin SM, Lin CJ, Hsu CW, et al: Prospective randomized controlled study of interferon-alpha in preventing hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors. Cancer. 100:376–382. 2004. View Article : Google Scholar
11	Qian J, Zhai A, Kao W, et al: Modulation of miR-122 on persistently Borna disease virus infected human oligodendroglial cells. Antiviral Res. 87:249–256. 2010. View Article : Google Scholar : PubMed/NCBI
12	Jopling CL, Yi M, Lancaster AM, Lemon SM and Sarnow P: Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science. 309:1577–1581. 2005. View Article : Google Scholar : PubMed/NCBI
13	Wu X, Wu S, Tong L, et al: miR-122 affects the viability and apoptosis of hepatocellular carcinoma cells. Scand J Gastroenterol. 44:1332–1339. 2009. View Article : Google Scholar : PubMed/NCBI
14	Coulouarn C, Factor VM, Andersen JB, Durkin ME and Thorgeirsson SS: Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene. 28:3526–3536. 2009. View Article : Google Scholar : PubMed/NCBI
15	Kirkwood J: Cancer immunotherapy: the interferon-alpha experience. Semin Oncol. 29(Suppl 7): 18–26. 2002. View Article : Google Scholar : PubMed/NCBI
16	Borden EC: Interferons - expanding therapeutic roles. N Engl J Med. 326:1491–1493. 1992. View Article : Google Scholar : PubMed/NCBI
17	Kirkwood JM, Ibrahim JG, Sondak VK, et al: High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol. 18:2444–2458. 2000.PubMed/NCBI
18	Wang P, Hou J, Lin L, et al: Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1. J Immunol. 185:6226–6233. 2010. View Article : Google Scholar : PubMed/NCBI
19	Hou J, Wang P, Lin L, et al: MicroRNA-146a feedback inhibits RIG-I-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol. 183:2150–2158. 2009. View Article : Google Scholar : PubMed/NCBI
20	Liu X, Zhan Z, Xu L, et al: MicroRNA-148/152 impair innate response and antigen presentation of TLR-triggered dendritic cells by targeting CaMKIIα. J Immunol. 185:7244–7251. 2010.PubMed/NCBI
21	Witwer KW, Sisk JM, Gama L and Clements JE: MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response. J Immunol. 184:2369–2376. 2010. View Article : Google Scholar : PubMed/NCBI
22	Kutay H, Bai S, Datta J, et al: Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem. 99:671–678. 2006. View Article : Google Scholar : PubMed/NCBI
23	Ma L, Liu J, Shen J, et al: Expression of miR-122 mediated by adenoviral vector induces apoptosis and cell cycle arrest of cancer cells. Cancer Biol Ther. 9:554–561. 2010. View Article : Google Scholar : PubMed/NCBI
24	Sarasin-Filipowicz M, Krol J, Markiewicz I, Heim MH and Filipowicz W: Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nat Med. 15:31–33. 2009. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Modulation of miR‑122 expression affects the interferon response in human hepatoma cells

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