Effect of evodiamine and berberine on the interaction between DNMTs and target microRNAs during malignant transformation of the colon by TGF-β1

Huang,Chao; Liu,Hong; Gong,Xiu-Li; Wu,Li-Yun; Wen,Bin

doi:10.3892/or.2017.5379

Effect of evodiamine and berberine on the interaction between DNMTs and target microRNAs during malignant transformation of the colon by TGF-β1

Authors:
- Chao Huang
- Hong Liu
- Xiu-Li Gong
- Li-Yun Wu
- Bin Wen
View Affiliations

Affiliations: Pi-Wei Institute, Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510000, P.R. China
Published online on: January 17, 2017 https://doi.org/10.3892/or.2017.5379
Pages: 1637-1645

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The tissue microenvironment functions as a crucial player in carcinogenesis, and transforming growth factor-β1 (TGF-β1) within the microenvironment stimulates the formation of neoplasms. Using an in vitro model of malignancy induced by TGF-β1, we assessed the effect of evodiamine and berberine on the interaction between DNA methyltransferases (DNMTs) and target microRNAs (miRNAs) in the model. Colon tissues from neonatal rats 7 days of age were cultured and malignancy was induced by TGF-β1 in vitro for 48 h, and then the tissues were respectively treated with evodiamine and berberine for 24 h. Morphological alteration of tissues was observed by an inverted microscope, histological structures were observed using hematoxylin and eosin staining, and the expression levels of DNMTs and targeted miRNAs screened by bioinformatics software combined with Gene chip analysis in our previous study were detected by immunohistochemistry and quantified by real-time PCR. Twenty-four hours after treatment with TGF-β1, expression levels of DNMT1, DNMT3A, DNMT3B and miR-152 (target DNMT1), miR-429 (target DNMT3A) and miR-29a (target DNMT3A/3B) were markedly decreased; however, after 48 h, the expression levels of DNMT1 and DNMT3A were significantly increased, but their target miRNAs were still decreased. After treatment with a DNMT inhibitor (5-Aza-dC), expression levels of the miRNAs were increased to a larger extent, but did not reach normal levels. After treatment with berberine and evodiamine for 24 h, respectively, increased expression of DNMT1, DNMT3A, DNMT3B and miR-152, miR-429, miR-29a was noted. In conclusion, the results of the present study suggest that miRNAs can also be post-transcriptionally regulated by their corresponding DNMTs and that berberine and evodiamine regulate the expression of these genes, which provides early epigenetic evidence for the prevention and therapy of colorectal cancer.

View Figures

View References

1	Tenesa A and Dunlop MG: New insights into the aetiology of colorectal cancer from genome-wide association studies. Nat Rev Genet. 10:353–358. 2009. View Article : Google Scholar : PubMed/NCBI
2	Friess H, Langrehr JM, Oettle H, Raedle J, Niedergethmann M, Dittrich C, Hossfeld DK, Stöger H, Neyns B, Herzog P, et al: A randomized multi-center phase II trial of the angiogenesis inhibitor cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer. BMC Cancer. 6:2852006. View Article : Google Scholar : PubMed/NCBI
3	Philip PA, Benedetti J, Corless CL, Wong R, O'Reilly EM, Flynn PJ, Rowland KM, Atkins JN, Mirtsching BC, Rivkin SE, et al: Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol. 28:3605–3610. 2010. View Article : Google Scholar : PubMed/NCBI
4	van Kampen JG, Marijnissen-van Zanten MA, Simmer F, van der Graaf WT, Ligtenberg MJ and Nagtegaal ID: Epigenetic targeting in pancreatic cancer. Cancer Treat Rev. 40:656–664. 2014. View Article : Google Scholar : PubMed/NCBI
5	Garagnani P, Pirazzini C and Franceschi C: Colorectal cancer microenvironment: Among nutrition, gut microbiota, inflammation and epigenetics. Curr Pharm Des. 19:765–778. 2013. View Article : Google Scholar : PubMed/NCBI
6	Postovit LM, Seftor EA, Seftor RE and Hendrix MJ: Influence of the microenvironment on melanoma cell fate determination and phenotype. Cancer Res. 66:7833–7836. 2006. View Article : Google Scholar : PubMed/NCBI
7	Adjei IM and Blanka S: Modulation of the tumor microenvironment for cancer treatment: A biomaterials approach. J Funct Biomater. 6:81–103. 2015. View Article : Google Scholar : PubMed/NCBI
8	Shi X and Wang X: The role of MTDH/AEG-1 in the progression of cancer. Int J Clin Exp Med. 8:4795–4807. 2015.PubMed/NCBI
9	Ma H, Xu H and Qin J: Biomimetic tumor microenvironment on a microfluidic platform. Biomicrofluidics. 7:115012013. View Article : Google Scholar : PubMed/NCBI
10	Schmaus A, Bauer J and Sleeman JP: Sugars in the microenvironment: The sticky problem of HA turnover in tumors. Cancer Metastasis Rev. 33:1059–1079. 2014. View Article : Google Scholar : PubMed/NCBI
11	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
12	Zu X, Zhang Q, Cao R, Liu J, Zhong J, Wen G and Cao D: Transforming growth factor-β signaling in tumor initiation, progression and therapy in breast cancer: An update. Cell Tissue Res. 347:73–84. 2012. View Article : Google Scholar : PubMed/NCBI
13	Neuzillet C, Tijeras-Raballand A, Cohen R, Cros J, Faivre S, Raymond E and de Gramont A: Targeting the TGFβ pathway for cancer therapy. Pharmacol Ther. 147:22–31. 2015. View Article : Google Scholar : PubMed/NCBI
14	Ohshio Y, Teramoto K, Hashimoto M, Kitamura S, Hanaoka J and Kontani K: Inhibition of transforming growth factor-β release from tumor cells reduces their motility associated with epithelial-mesenchymal transition. Oncol Rep. 30:1000–1006. 2013.PubMed/NCBI
15	Mao Y, Keller ET, Garfield DH, Shen K and Wang J: Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev. 32:303–315. 2013. View Article : Google Scholar : PubMed/NCBI
16	Quante M, Varga J, Wang TC and Greten FR: The gastrointestinal tumor microenvironment. Gastroenterology. 145:63–78. 2013. View Article : Google Scholar : PubMed/NCBI
17	Lee JY, Jeong W, Lim W, Lim CH, Bae SM, Kim J, Bazer FW and Song G: Hypermethylation and post-transcriptional regulation of DNA methyltransferases in the ovarian carcinomas of the laying hen. PLoS One. 8:e616582013. View Article : Google Scholar : PubMed/NCBI
18	Xue G, Ren Z, Chen Y, Zhu J, Du Y, Pan D, Li X and Hu B: A feedback regulation between miR-145 and DNA methyltransferase 3b in prostate cancer cell and their responses to irradiation. Cancer Lett. 361:121–127. 2015. View Article : Google Scholar : PubMed/NCBI
19	He L and Hannon GJ: MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet. 5:522–531. 2004. View Article : Google Scholar : PubMed/NCBI
20	Mendell JT: MicroRNAs: Critical regulators of development, cellular physiology and malignancy. Cell Cycle. 4:1179–1184. 2005. View Article : Google Scholar : PubMed/NCBI
21	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
22	Vaiopoulos AG, Athanasoula KCh and Papavassiliou AG: NF-κB in colorectal cancer. J Mol Med. 91:1029–1037. 2013. View Article : Google Scholar : PubMed/NCBI
23	Hamidi T, Singh AK and Chen T: Genetic alterations of DNA methylation machinery in human diseases. Epigenomics. 7:247–265. 2015. View Article : Google Scholar : PubMed/NCBI
24	Cea M, Cagnetta A, Gobbi M, Patrone F, Richardson PG, Hideshima T and Anderson KC: New insights into the treatment of multiple myeloma with histone deacetylase inhibitors. Curr Pharm Des. 19:734–744. 2013. View Article : Google Scholar : PubMed/NCBI
25	Andreoli F, Barbosa AJ, Parenti MD and Del Rio A: Modulation of epigenetic targets for anticancer therapy: Clinicopathological relevance, structural data and drug discovery perspectives. Curr Pharm Des. 19:578–613. 2013. View Article : Google Scholar : PubMed/NCBI
26	Esteller M: Epigenetics in cancer. N Engl J Med. 358:1148–1159. 2008. View Article : Google Scholar : PubMed/NCBI
27	Laird PW: The power and the promise of DNA methylation markers. Nat Rev Cancer. 3:253–266. 2003. View Article : Google Scholar : PubMed/NCBI
28	Markowitz SD and Bertagnolli MM: Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med. 361:2449–2460. 2009. View Article : Google Scholar : PubMed/NCBI
29	Wu Q and Ni X: ROS-mediated DNA methylation pattern alterations in carcinogenesis. Curr Drug Targets. 16:13–19. 2015. View Article : Google Scholar : PubMed/NCBI
30	Luczak MW and Jagodziński PP: The role of DNA methylation in cancer development. Folia Histochem Cytobiol. 44:143–154. 2006.PubMed/NCBI
31	Pastuszak-Lewandoska D, Kordiak J, Migdalska-Sęk M, Czarnecka KH, Antczak A, Górski P, Nawrot E, Kiszałkiewicz JM, Domańska D and Brzeziańska-Lasota E: Quantitative analysis of mRNA expression levels and DNA methylation profiles of three neighboring genes: FUS1NPRL2/G21 and RASSF1A in non-small cell lung cancer patients. Respir Res. 16:762015. View Article : Google Scholar : PubMed/NCBI
32	Garzon R, Fabbri M, Cimmino A, Calin GA and Croce CM: MicroRNA expression and function in cancer. Trends Mol Med. 12:580–587. 2006. View Article : Google Scholar : PubMed/NCBI
33	Xiong Y, Fang JH, Yun JP, Yang J, Zhang Y, Jia WH and Zhuang SM: Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology. 51:836–845. 2010.PubMed/NCBI
34	Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, et al: MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA. 104:15805–15810. 2007. View Article : Google Scholar : PubMed/NCBI
35	Xu H, Cheung IY, Guo HF and Cheung NK: MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: Potential implications for immune based therapy of human solid tumors. Cancer Res. 69:6275–6281. 2009. View Article : Google Scholar : PubMed/NCBI
36	Ji W, Yang L, Yuan J, Yang L, Zhang M, Qi D, Duan X, Xuan A, Zhang W, Lu J, et al: MicroRNA-152 targets DNA methyltransferase 1 in NiS-transformed cells via a feedback mechanism. Carcinogenesis. 34:446–453. 2013. View Article : Google Scholar : PubMed/NCBI
37	Langhe R, Norris L, Saadeh FA, Blackshields G, Varley R, Harrison A, Gleeson N, Spillane C, Martin C, O'Donnell DM, et al: A novel serum microRNA panel to discriminate benign from malignant ovarian disease. Cancer Lett. 356:628–636. 2015. View Article : Google Scholar : PubMed/NCBI
38	Pinto R, De Summa S, Danza K, Popescu O, Paradiso A, Micale L, Merla G, Palumbo O, Carella M and Tommasi S: MicroRNA expression profiling in male and female familial breast cancer. Br J Cancer. 111:2361–2368. 2014. View Article : Google Scholar : PubMed/NCBI
39	Omrane I and Benammar-Elgaaied A: The immune microenvironment of the colorectal tumor: Involvement of immunity genes and microRNAs belonging to the TH17 pathway. Biochim Biophys Acta. 1856:28–38. 2015.PubMed/NCBI
40	Slaby O, Svoboda M, Michalek J and Vyzula R: MicroRNAs in colorectal cancer: Translation of molecular biology into clinical application. Mol Cancer. 8:1022009. View Article : Google Scholar : PubMed/NCBI
41	Chen C, Yu Z, Li Y, Fichna J and Storr M: Effects of berberine in the gastrointestinal tract - a review of actions and therapeutic implications. Am J Chin Med. 42:1053–1070. 2014. View Article : Google Scholar : PubMed/NCBI
42	Wang L, Cao H, Lu N, Liu L, Wang B, Hu T, Israel DA, Peek RM Jr, Polk DB and Yan F: Berberine inhibits proliferation and down-regulates epidermal growth factor receptor through activation of Cbl in colon tumor cells. PLoS One. 8:e566662013. View Article : Google Scholar : PubMed/NCBI
43	Park JJ, Seo SM, Kim EJ, Lee YJ, Ko YG, Ha J and Lee M: Berberine inhibits human colon cancer cell migration via AMP-activated protein kinase-mediated downregulation of integrin β1 signaling. Biochem Biophys Res Commun. 426:461–467. 2012. View Article : Google Scholar : PubMed/NCBI
44	Murthy KN Chidambara, Jayaprakasha GK and Patil BS: The natural alkaloid berberine targets multiple pathways to induce cell death in cultured human colon cancer cells. Eur J Pharmacol. 688:14–21. 2012. View Article : Google Scholar : PubMed/NCBI
45	Kan SF, Yu CH, Pu HF, Hsu JM, Chen MJ and Wang PS: Anti-proliferative effects of evodiamine on human prostate cancer cell lines DU145 and PC3. J Cell Biochem. 101:44–56. 2007. View Article : Google Scholar : PubMed/NCBI
46	Kobayashi Y: The nociceptive and anti-nociceptive effects of evodiamine from fruits of Evodia rutaecarpa in mice. Planta Med. 69:425–428. 2003. View Article : Google Scholar : PubMed/NCBI
47	Chien CC, Wu MS, Shen SC, Ko CH, Chen CH, Yang LL and Chen YC: Activation of JNK contributes to evodiamine-induced apoptosis and G2/M arrest in human colorectal carcinoma cells: A structure-activity study of evodiamine. PLoS One. 9:e997292014. View Article : Google Scholar : PubMed/NCBI