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Association between microRNA‑527 and glypican‑3 in hepatocellular carcinoma

野村 圭 香川大学 DOI:10.3892/ol.2021.12490

2020.09.16

概要

The present study aimed to identify the specific microRNAs (miRNAs/miRs) and their corresponding target genes involved in hepatocellular carcinomas (HCCs). Microarray analysis was performed to examine the miRNA expression profiles of four paired HCC and corresponding non‑cancerous (N) liver tissues using 985 miRNA probes. The Human miRNA Target database was used to identify the target genes of differentially expressed miRNAs between the HCC and N tissues. The protein expression levels of target genes in the HCC tissues and cell lines were evaluated using western blotting. miRNA‑mediated suppression of target gene expression was evaluated by transiently transfecting the miRNA into the HCC cell lines. Of the 985 miRNAs evaluated, four miRNAs were differentially expressed (three upregulated and one downregulated miRNAs). Of these four miRNAs, miRNA‑527 was highly downregulated in the HCC tissues. Glypican‑3 (GPC‑3) was predicted as a target gene of miRNA‑527. Western blotting revealed that GPC‑3 protein is highly expressed in the HCC tissues and HCC cell lines compared with N and normal cell lines. Transfection with miR‑527 resulted in suppression of GPC‑3 protein expression in the Cos7 cells. Furthermore, transfection with miR‑527 also inhibited the intrinsic expression of GPC‑3 in the Huh‑7 cell line. This indicated that miR‑527 in the HCC tissues may be an important novel miRNA that targets the GPC‑3 gene expression. GPC‑3, whose expression is regulated by miR‑527, may be involved in the development and progression of HCC.

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参考文献

1. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A and

Roberts LR: A global view of hepatocellular carcinoma: Trends,

risk, prevention and management. Nat Rev Gastroenterol

Hepatol 16: 589‑604, 2019.

2. Wang CH, Wey KC, Mo LR, Chang KK, Lin RC and Kuo JJ:

Current trends and recent advances in diagnosis, therapy, and

prevention of hepatocellular carcinoma. Asian Pac J Cancer

Prev 16: 3595‑3604, 2015.

3. Sherman M: Hepatocellular carcinoma: Epidemiology,

surveillance, and diagnosis. Semin Liver Dis 30: 3‑16, 2010.

4. Iwama H, Masaki T and Kuriyama S: Abundance of microRNA

target motifs in the 3'‑UTRs of 20527 human genes. FEBS

Lett 581: 1805‑1810, 2007.

5. Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and

function. Cell 116: 281‑297, 2004.

6. Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ,

MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, et al:

Combinatorial microRNA target predictions. Nat Genet 37:

495‑500, 2005.

7. Bartel DP: Metazoan MicroRNAs. Cell 173: 20‑51, 2018.

8. Tomasello L, Cluts L and Croce CM: Experimental validation

of microRNA targets: Mutagenesis of binding regions. Methods

Mol Biol 1970: 331‑339, 2019.

9. Meng F, Henson R, Wehbe‑Janek H, Ghoshal K, Jacob ST

and Patel T: MicroRNA‑21 regulates expression of the PTEN

tumor suppressor gene in human hepatocellular cancer.

Gastroenterology 133: 647‑658, 2007.

10. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H,

Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, et al:

Reduced expression of the let‑7 microRNAs in human lung

cancers in association with shortened postoperative survival.

Cancer Res 64: 3753‑3756, 2004.

11. Varnholt H, Drebber U, Schulze F, Wedemeyer I, Schirmacher P,

Dienes HP and Odenthal M: MicroRNA gene expression profile

of hepatitis C virus‑associated hepatocellular carcinoma.

Hepatology 47: 1223‑1232, 2008.

12. Visone R and Croce CM: miRNAs and cancer. Am J Pathol 174:

1131‑1138, 2009.

13. Morishita A and Masaki T: miRNA in hepatocellular carcinoma.

Hepatol Res 45: 128‑141, 2015.

14. Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD,

Shimizu M, Cimmino A, Zupo S, Dono M, et al: MicroRNA

profiling reveals distinct signatures in B cell chronic lymphocytic

leukemias. Proc Natl Acad Sci USA 101: 11755‑11760, 2004.

15. Sevignani C, Calin GA, Siracusa LD and Croce CM: Mammalian

microRNAs: A small world for fine‑tuning gene expression.

Mamm Genome 17: 189‑202, 2006.

16. Metzler M, Wilda M, Busch K, Viehmann S and Borkhardt A:

High expression of precursor microRNA‑155/BIC RNA

in children with Burkitt lymphoma. Genes Chromosomes

Cancer 39: 167‑169, 2004.

17. Michael MZ, O' Connor SM, van Holst Pellekaan NG, Young GP

and James RJ: Reduced accumulation of specific microRNAs in

colorectal neoplasia. Mol Cancer Res 1: 882‑891, 2003.

18. Tokarz P and Blasiak J: The role of microRNA in metastatic

colorectal cancer and its significance in cancer prognosis and

treatment. Acta Biochim Pol 59: 467‑474, 2012.

19. Del Vescovo V and Denti MA: microRNA and lung cancer. Adv

Exp Med Biol 889: 153‑177, 2015.

20. Yang X, Liang L, Zhang XF, Jia HL, Qin Y, Zhu XC, Gao XM,

Qiao P, Zheng Y, Sheng YY, et al: MicroRNA‑26a suppresses

tumor growth and metastasis of human hepatocellular carcinoma

by targeting interleukin‑6‑Stat3 pathway. Hepatology 58:

158‑170, 2013.

21. Zhu Y, Lu Y, Zhang Q, Liu JJ, Li TJ, Yang JR, Zeng C and

Zhuang SM: MicroRNA‑26a/b and their host genes cooperate to

inhibit the G1/S transition by activating the pRb protein. Nucleic

Acids Res 40: 4615‑4625, 2012.

22. Wang Y, Lu Y, Toh ST, Sung WK, Tan P, Chow P, Chung AYF,

Jooi LLP and Lee CG: Lethal‑7 is down‑regulated by the

hepatitis B virus x protein and targets signal transducer and

activator of transcription 3. J Hepatol 53: 57‑66, 2010.

23. Wang Z, Lin S, Li JJ, Xu Z, Yao H, Zhu X, Xie D, Shen Z, Sze J,

Li K, et al: MYC protein inhibits transcription of the microRNA

cluster MC‑let‑7a‑1~let‑7d via noncanonical E‑box. J Biol

Chem 286: 39703‑39714, 2011.

24. Tsang WP and Kwok TT: Let‑7a microRNA suppresses

therapeutics‑induced cancer cell death by targeting caspase‑3.

Apoptosis 13: 1215‑1222, 2008.

25. Di Fazio P, Montalbano R, Neureiter D, Alinger B, Schmidt A,

Merkel AL, Quint K and Ocker M: Downregulation of HMGA2

by the pan‑deacetylase inhibitor panobinostat is dependent on

hsa‑let‑7b expression in liver cancer cell lines. Exp Cell Res 318:

1832‑1843, 2012.

NOMURA et al: ASSOCIATION BETWEEN miR‑527 AND GLYPICAN‑3 IN HEPATOCELLULAR CARCINOMA

26. Zhu XM, Wu LJ, Xu J, Yang R and Wu FS: Let‑7c microRNA

expression and clinical significance in hepatocellular carcinoma.

J Int Med Res 39: 2323‑2329, 2011.

27. Lan FF, Wang H, Chen YC, Chan CY, Ng SS, Li K, Xie D,

He ML, Lin MC and Kung HF: Hsa‑let‑7g inhibits proliferation

of hepatocellular carcinoma cells by downregulation of c‑Myc

and upregulation of p16(INK4A). Int J Cancer 128: 319‑331,

2011.

28. Traister A, Shi W and Filmus J: Mammalian Notum induces the

release of glypicans and other GPI‑anchored proteins from the

cell surface. Biochem J 410: 503‑511, 2008.

29. Li N, Gao W, Zhang YF and Ho M: Glypicans as Cancer

Therapeutic Targets. Trends Cancer 4: 741‑754, 2018.

30. Capurro MI, Xu P, Shi W, Li F, Jia A and Filmus J: Glypican‑3

inhibits Hedgehog signaling during development by competing

with patched for Hedgehog binding. Dev Cell 14: 700‑711,

2008.

31. Shirakawa H, Suzuki H, Shimomura M, Kojima M, Gotohda N,

Takahashi S, Nakagohri T, Konishi M, Kobayashi N,

Kinoshita T, et al: Glypican‑3 expression is correlated with poor

prognosis in hepatocellular carcinoma. Cancer Sci 100: 1403‑1407,

2009.

32. Zhang J, Zhang M, Ma H, Song X, He L, Ye X and Li X:

Overexpression of glypican‑3 is a predictor of poor prognosis in

hepatocellular carcinoma: An updated meta‑analysis. Medicine

(Baltimore) 97: e11130, 2018.

33. Fujihara S, Kato K, Morishita A, Iwama H, Nishioka T, Chiyo T,

Nishiyama N, Miyoshi H, Kobayashi M, Kobara H, et al:

Antidiabetic drug metformin inhibits esophageal adenocar‑

cinoma cell proliferation in vitro and in vivo. Int J Oncol 46:

2172‑2180, 2015.

34. Fujita K, Iwama H, Sakamoto T, Okura R, Kobayashi K, Takano J,

Katsura A, Tatsuta M, Maeda E, Mimura S, et al: Galectin‑9

suppresses the growth of hepatocellular carcinoma via apoptosis

in vitro and in vivo. Int J Oncol 46: 2419‑2430, 2015.

35. Bolstad BM, Irizarry RA, Astrand M and Speed TP: A comparison

of normalization methods for high density oligonucleotide array

data based on variance and bias. Bioinformatics 19: 185‑193,

2003.

36. Laemmli UK: Cleavage of structural proteins during the

assembly of the head of bacteriophage T4. Nature 227: 680‑685,

1970.

37. Towbin H, Staehelin T and Gordon J: Electrophoretic transfer

of proteins from polyacrylamide gels to nitrocellulose sheets:

Procedure and some applications. Proc Natl Acad Sci USA 76:

4350‑4354, 1979.

38. Benjamini Y and Hochberg Y: Controlling the false discovery

rate: A practical and powerful approach to multiple testing.

J R Stat Soc B 57: 289‑300, 1995.

39. Chen Y‑H, Song Y, Yu YL, Cheng W and Tong X: miRNA‑10a

promotes cancer cell proliferation in oral squamous cell

carcinoma by upregulating GLUT1 and promoting glucose

metabolism. Oncol Lett 17: 5441‑5446, 2019.

40. Pal R and Greene S: microRNA‑10b is overexpressed and critical

for cell survival and proliferation in medulloblastoma. PLoS

One 10: e0137845, 2015.

41. Werk AN, Bruckmueller H, Haenisch S and Cascorbi I: Genetic

variants may play an important role in mRNA‑miRNA inter‑

action: Evidence for haplotype‑dependent downregulation of

ABCC2 (MRP2) by miRNA‑379. Pharmacogenet Genomics 24:

283‑291, 2014.

42. Nishida T and Kataoka H: Glypican 3‑targeted therapy in hepa‑

tocellular carcinoma. Cancers (Basel) 11: E1339, 2019.

43. Vongchan P and Linhardt RJ: Characterization of a new mono‑

clonal anti‑glypican‑3 antibody specific to the hepatocellular

carcinoma cell line, HepG2. World J Hepatol 9: 368‑384, 2017.

44. Singh AK, Kumar R and Pandey AK: Hepatocellular Carcinoma:

Causes, Mechanism of Progression and Biomarkers. Curr Chem

Genomics Transl Med 12: 9‑26, 2018.

45. Zhou F, Shang W, Yu X and Tian J: Glypican‑3: A promising

biomarker for hepatocellular carcinoma diagnosis and treatment.

Med Res Rev 38: 741‑767, 2018.

46. Wang L, Yao M, Pan LH, Qian Q and Yao DF: Glypican‑3 is a

biomarker and a therapeutic target of hepatocellular carcinoma.

Hepatobiliary Pancreat Dis Int 14: 361‑366, 2015.

47. Lai JP, Sandhu DS, Yu C, Han T, Moser CD, Jackson KK,

Guerrero RB, Aderca I, Isomoto H, Garrity‑Park MM, et al:

Sulfatase 2 up‑regulates glypican 3, promotes fibroblast growth

factor signaling, and decreases survival in hepatocellular

carcinoma. Hepatology 47: 1211‑1222, 2008.

48. Huo W, Zhu XM, Pan XY, Du M, Sun Z and Li ZM: MicroRNA‑527

inhibits TGF‑β/SMAD induced epithelial‑mesenchymal tran‑

sition via downregulating SULF2 expression in non‑small‑cell

lung cancer. Math Biosci Eng 16: 4607‑4621, 2019.

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