Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Digestive Diseases and Sciences
Erschienen in: Digestive Diseases and Sciences 6/2014

01.06.2014 | Review

microRNA: A Promising Diagnostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma

verfasst von: Xiaofei Li, Wenjun Yang, Lianqing Lou, Yongxin Chen, Shuang Wu, Guoqiang Ding

Erschienen in: Digestive Diseases and Sciences | Ausgabe 6/2014

Einloggen, um Zugang zu erhalten

Abstract

microRNAs constitute a novel class of small, non-coding RNAs that negatively regulate gene expression via translational inhibition or mRNA degradation. Aberrant miRNA expression has been implicated in the initiation, progression, and metastasis of hepatocellular carcinoma (HCC). It is well-documented that miRNAs function as either tumor suppressor genes or oncogenes in the development and progression of HCC. Additionally, substantial evidence suggests that unique miRNA signatures can serve as valuable diagnostic and prognostic biomarkers for HCC. Interestingly, certain subsets of miRNAs have also been identified as potential therapeutic targets for HCC.
Literatur
1.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN. Int J Cancer. 2008;2010:2893–2917.
2.
Gomaa AI, Khan SA, Toledano MB, Waked I, Taylor-Robinson SD. Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol. 2008;14:4300–4308.PubMedCentralPubMedCrossRef
3.
4.
Ray K. Liver cancer: the promise of new approaches in the management of hepatocellular carcinoma—adding to the toolbox? Nat Rev Gastroenterol Hepatol. 2013;10:195.PubMedCrossRef
5.
Trinchet JC, Chaffaut C, Bourcier V, et al. Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities. Hepatology. 2011;54:1987–1997.PubMedCrossRef
6.
Qu KZ, Zhang K, Li H, Afdhal NH, Albitar M. Circulating microRNAs as biomarkers for hepatocellular carcinoma. J Clin Gastroenterol. 2011;45:355–360.PubMedCrossRef
7.
8.
9.
Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003;17:3011–3016.PubMedCentralPubMedCrossRef
10.
Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 2005;123:631–640.PubMedCrossRef
11.
Calin GA, Sevignani C, Dumitru CD, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 2004;101:2999–3004.PubMedCentralPubMedCrossRef
12.
Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007;302:1–12.PubMedCrossRef
13.
14.
15.
Danial NN. BCL-2 family proteins: critical checkpoints of apoptotic cell death. Clin Cancer Res. 2007;13:7254–7263.PubMedCrossRef
16.
Li Y, Tan W, Neo TW, et al. Role of the miR-106b-25 microRNA cluster in hepatocellular carcinoma. Cancer Sci. 2009;100:1234–1242.PubMedCrossRef
17.
Gramantieri L, Fornari F, Ferracin M, et al. MicroRNA-221 targets Bmf in hepatocellular carcinoma and correlates with tumor multifocality. Clin Cancer Res. 2009;15:5073–5081.PubMedCentralPubMedCrossRef
18.
Xiong Y, Fang JH, Yun JP, et al. Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology. 2010;51:836–845.PubMed
19.
Su H, Yang JR, Xu T, et al. MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res. 2009;69:1135–1142.PubMedCrossRef
20.
Lin CJ, Gong HY, Tseng HC, Wang WL, Wu JL. miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines. Biochem Biophys Res Commun. 2008;375:315–320.PubMedCrossRef
21.
Garofalo M, Di Leva G, Romano G, et al. miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell. 2009;16:498–509.PubMedCentralPubMedCrossRef
22.
Robertson SC, Tynan JA, Donoghue DJ. RTK mutations and human syndromes: when good receptors turn bad. Trends Genet. 2000;16:265–271.PubMedCrossRef
23.
24.
Ueki T, Fujimoto J, Suzuki T, Yamamoto H, Okamoto E. Expression of hepatocyte growth factor and its receptor c-met proto-oncogene in hepatocellular carcinoma. Hepatology. 1997;25:862–866.PubMedCrossRef
25.
Datta J, Kutay H, Nasser MW, et al. Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis. Cancer Res. 2008;68:5049–5058.PubMedCentralPubMedCrossRef
26.
Salvi A, Sabelli C, Moncini S, et al. MicroRNA-23b mediates urokinase and c-met downmodulation and a decreased migration of human hepatocellular carcinoma cells. FEBS J. 2009;276:2966–2982.PubMedCrossRef
27.
Li N, Fu H, Tie Y, et al. miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett. 2009;275:44–53.PubMedCrossRef
28.
Jang JY, Lee YS, Jeon YK, Lee K, Jang JJ, Kim CW. ANT2 suppression by shRNA restores miR-636 expression, thereby downregulating Ras and inhibiting tumorigenesis of hepatocellular carcinoma. Exp Mol Med. 2013;45:e3.PubMedCentralPubMedCrossRef
29.
30.
Vinciguerra M, Sgroi A, Veyrat-Durebex C, Rubbia-Brandt L, Buhler LH, Foti M. Unsaturated fatty acids inhibit the expression of tumor suppressor phosphatase and tensin homolog (PTEN) via microRNA-21 up-regulation in hepatocytes. Hepatology. 2009;49:1176–1184.PubMedCrossRef
31.
Matsushime H, Quelle DE, Shurtleff SA, Shibuya M, Sherr CJ, Kato JY. D-type cyclin-dependent kinase activity in mammalian cells. Mol Cell Biol. 1994;14:2066–2076.PubMedCentralPubMed
32.
Resnitzky D, Reed SI. Different roles for cyclins D1 and E in regulation of the G1-to-S transition. Mol Cell Biol. 1995;15:3463–3469.PubMedCentralPubMed
33.
Bloom J, Cross FR. Multiple levels of cyclin specificity in cell-cycle control. Nat Rev Mol Cell Biol. 2007;8:149–160.PubMedCrossRef
34.
Kota J, Chivukula RR, O’Donnell KA, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009;137:1005–1017.PubMedCentralPubMedCrossRef
35.
Xu T, Zhu Y, Xiong Y, Ge YY, Yun JP, Zhuang SM. MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology. 2009;50:113–121.PubMedCrossRef
36.
Xiao F, Zhang W, Chen L, et al. MicroRNA-503 inhibits the G1/S transition by downregulating cyclin D3 and E2F3 in hepatocellular carcinoma. J Transl Med. 2013;11:195.PubMedCentralPubMedCrossRef
37.
Fornari F, Gramantieri L, Ferracin M, et al. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene. 2008;27:5651–5661.PubMedCrossRef
38.
Chen J, Zhang B, Wong N, et al. Sirtuin 1 is upregulated in a subset of hepatocellular carcinomas where it is essential for telomere maintenance and tumor cell growth. Cancer Res. 2011;71:4138–4149.PubMedCrossRef
39.
Bae HJ, Noh JH, Kim JK, et al. MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma. Oncogene. 2013. doi:10.​1038/​onc.​2013.​216.
40.
Lim L, Balakrishnan A, Huskey N, et al. MicroRNA-494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer. Hepatology. 2014;59:202–215.
41.
Matsumine A, Senda T, Baeg GH, et al. MCC, a cytoplasmic protein that blocks cell cycle progression from the G0/G1 to S phase. J Biol Chem. 1996;271:10341–10346.PubMedCrossRef
42.
Liu RF, Xu X, Huang J, et al. Down-regulation of miR-517a and miR-517c promotes proliferation of hepatocellular carcinoma cells via targeting Pyk2. Cancer Lett. 2013;329:164–173.PubMedCrossRef
43.
Wong QW, Lung RW, Law PT, et al. MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. Gastroenterology. 2008;135:257–269.PubMedCrossRef
44.
Tsai WC, Hsu PW, Lai TC, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009;49:1571–1582.PubMedCrossRef
45.
Ji J, Zhao L, Budhu A, et al. Let-7g targets collagen type I alpha2 and inhibits cell migration in hepatocellular carcinoma. J Hepatol. 2010;52:690–697.PubMedCentralPubMedCrossRef
46.
Yao J, Liang L, Huang S, et al. MicroRNA-30d promotes tumor invasion and metastasis by targeting Galphai2 in hepatocellular carcinoma. Hepatology. 2010;51:846–856.PubMed
47.
Ding J, Huang S, Wu S, et al. Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA. Nat Cell Biol. 2010;12:390–399.PubMedCrossRef
48.
Dovas A, Couchman JR. RhoGDI: multiple functions in the regulation of Rho family GTPase activities. Biochem J. 2005;390:1–9.PubMedCentralPubMed
49.
50.
Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006.PubMedCrossRef
51.
Xi Y, Nakajima G, Gavin E, et al. Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA. 2007;13:1668–1674.PubMedCentralPubMedCrossRef
52.
Li LM, Hu ZB, Zhou ZX, et al. Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma. Cancer Res. 2010;70:9798–9807.PubMedCrossRef
53.
Zhou J, Yu L, Gao X, et al. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29:4781–4788.CrossRef
54.
Varnholt H, Drebber U, Schulze F, et al. MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatology. 2008;47:1223–1232.PubMedCrossRef
55.
Ladeiro Y, Couchy G, Balabaud C, et al. MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatology. 2008;47:1955–1963.PubMedCrossRef
56.
Yamashita T, Ji J, Budhu A, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 2009;136:1012–1024.PubMedCentralPubMedCrossRef
57.
Ji J, Yamashita T, Budhu A, et al. Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology. 2009;50:472–480.PubMedCentralPubMedCrossRef
58.
Borel F, Konstantinova P, Jansen PL. Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma. J Hepatol. 2012;56:1371–1383.PubMedCrossRef
59.
Qin LX, Tang ZY. The prognostic molecular markers in hepatocellular carcinoma. World J Gastroenterol. 2002;8:385–392.PubMed
60.
Tannapfel A, Grund D, Katalinic A, et al. Decreased expression of p27 protein is associated with advanced tumor stage in hepatocellular carcinoma. Int J Cancer. 2000;89:350–355.PubMedCrossRef
61.
Watanabe J, Kushihata F, Honda K, et al. Prognostic significance of Bcl-xL in human hepatocellular carcinoma. Surgery. 2004;135:604–612.PubMedCrossRef
62.
Ura S, Honda M, Yamashita T, et al. Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma. Hepatology. 2009;49:1098–1112.PubMedCrossRef
63.
Budhu A, Jia HL, Forgues M, et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology. 2008;47:897–907.PubMedCrossRef
64.
Nakamura M, Nagano H, Marubashi S, et al. Pilot study of combination chemotherapy of S-1, a novel oral DPD inhibitor, and interferon-alpha for advanced hepatocellular carcinoma with extrahepatic metastasis. Cancer. 2008;112:1765–1771.PubMedCrossRef
65.
Nagano H, Miyamoto A, Wada H, et al. Interferon-alpha and 5-fluorouracil combination therapy after palliative hepatic resection in patients with advanced hepatocellular carcinoma, portal venous tumor thrombus in the major trunk, and multiple nodules. Cancer. 2007;110:2493–2501.PubMedCrossRef
66.
Kubo S, Nishiguchi S, Hirohashi K, et al. Effects of long-term postoperative interferon-alpha therapy on intrahepatic recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. A randomized, controlled trial. Ann Intern Med. 2001;134:963–967.PubMedCrossRef
67.
Shiratori Y, Shiina S, Teratani T, et al. Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus. Ann Intern Med. 2003;138:299–306.PubMedCrossRef
68.
69.
Tomimaru Y, Eguchi H, Nagano H, et al. MicroRNA-21 induces resistance to the anti-tumour effect of interferon-alpha/5-fluorouracil in hepatocellular carcinoma cells. Br J Cancer. 2010;103:1617–1626.PubMedCentralPubMedCrossRef
70.
Tomokuni A, Eguchi H, Tomimaru Y, et al. miR-146a suppresses the sensitivity to interferon-alpha in hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2011;414:675–680.PubMedCrossRef
71.
Ye QH, Qin LX, Forgues M, et al. Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med. 2003;9:416–423.PubMedCrossRef
72.
Sun BS, Dong QZ, Ye QH, et al. Lentiviral-mediated miRNA against osteopontin suppresses tumor growth and metastasis of human hepatocellular carcinoma. Hepatology. 2008;48:1834–1842.PubMedCrossRef
73.
Arzumanyan A, Reis HM, Feitelson MA. Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat Rev Cancer. 2013;13:123–135.PubMedCrossRef
74.
Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science. 2005;309:1577–1581.PubMedCrossRef
75.
Lanford RE, Hildebrandt-Eriksen ES, Petri A, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science. 2010;327:198–201.PubMedCentralPubMedCrossRef
76.
Wang B, Hsu SH, Majumder S, et al. TGFbeta-mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3. Oncogene. 2010;29:1787–1797.PubMedCentralPubMedCrossRef
77.
Fornari F, Gramantieri L, Giovannini C, et al. MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res. 2009;69:5761–5767.PubMedCrossRef
78.
Bai S, Nasser MW, Wang B, et al. MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem. 2009;284:32015–32027.PubMedCentralPubMedCrossRef
79.
80.
Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet. 2003;4:346–358.PubMedCrossRef
81.
Sobrevals L, Enguita M, Rodriguez C, et al. AAV vectors transduce hepatocytes in vivo as efficiently in cirrhotic as in healthy rat livers. Gene Ther. 2012;19:411–417.PubMedCrossRef
82.
Turner P, Petch A, Al-Rubeai M. Encapsulation of viral vectors for gene therapy applications. Biotechnol Prog. 2007;23:423–429.PubMedCrossRef
83.
Kim J, Kim PH, Kim SW, Yun CO. Enhancing the therapeutic efficacy of adenovirus in combination with biomaterials. Biomaterials. 2012;33:1838–1850.PubMedCentralPubMedCrossRef
84.
Yilmazer A, Al-Jamal WT, Van den Bossche J, Kostarelos K. The effect of artificial lipid envelopment of Adenovirus 5 (Ad5) on liver de-targeting and hepatotoxicity. Biomaterials. 2013;34:1354–1363.PubMedCrossRef
85.
Pereira DM, Rodrigues PM, Borralho PM, Rodrigues CM. Delivering the promise of miRNA cancer therapeutics. Drug Discov Today. 2013;18:282–289.PubMedCrossRef
86.
Takeshita F, Minakuchi Y, Nagahara S, et al. Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo. Proc Natl Acad Sci USA. 2005;102:12177–12182.PubMedCentralPubMedCrossRef
87.
Germer K, Leonard M, Zhang X. RNA aptamers and their therapeutic and diagnostic applications. Int J Biochem Mol Biol. 2013;4:27–40.PubMedCentralPubMed
88.
89.
O’Neill LA, Sheedy FJ, McCoy CE. MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat Rev Immunol. 2011;11:163–175.PubMedCrossRef
Metadaten
Titel
microRNA: A Promising Diagnostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma
verfasst von
Xiaofei Li
Wenjun Yang
Lianqing Lou
Yongxin Chen
Shuang Wu
Guoqiang Ding
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 6/2014
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-013-3006-1

Weitere Artikel der Ausgabe 6/2014

Digestive Diseases and Sciences 6/2014 Zur Ausgabe

UNM Clinical Case Conferences

Colitis Associated with Biological Agents

Original Article

Factors Affecting First-Line Triple Therapy of Helicobacter pylori Including CYP2C19 Genotype and Antibiotic Resistance

Editorial

An ALTernate Interpretation of Serum Transaminases

Original Article

Clinical Impact of Predicting CCND1 Amplification Using Plasma DNA in Superficial Esophageal Squamous Cell Carcinoma

Editorial

Gastric Intestinal Metaplasia and Tamoxifen: Can We Reverse the Inevitable?

Original Article

Thiopurine S-methyltransferase (TPMT) Activity Is Better Determined by Biochemical Assay Versus Genotyping in the Jewish Population

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise