Current issue
Archive
Manuscripts accepted
About the Journal
Editorial office
Editorial board
Section Editors
Abstracting and indexing
Subscription
Contact
Ethical standards and procedures
Most read articles
Instructions for authors
Article Processing Charge (APC)
Regulations of paying article processing charge (APC)
RENAL CANCER / BASIC RESEARCH
Curcumin affects the prognosis of renal cell carcinoma through a negative feedback loop of H19/miR-675/HDAC/CTCF
1
Zhejiang Pharmaceutical College, Ningbo, Zhejiang, China
2
College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
Submission date: 2019-09-07
Final revision date: 2020-02-01
Acceptance date: 2020-03-12
Online publication date: 2021-04-04
Arch Med Sci 2025;21(4):1556-1566
KEYWORDS
TOPICS
ABSTRACT
Introduction:
The objective of this study was to explore the role of curcumin (CUR) in the control of renal cell carcinoma (RCC) as well as the molecular mechanism underlying the effect of CUR.
Material and methods:
Real-time PCR, Western blot analysis, immunohistochemistry (IHC) assay, and luciferase assay were utilized to detect the effect of CUR.
Results:
Mesoscale nanoparticles (particles) could be safely and preferentially accumulated in the kidney in a dose-dependent manner, and the specific localization of particles in the kidney reached its maximum level at a dose of 25 mg/kg. Treatment with CUR alleviated RCC by up-regulating the expression of H19 and miR-675 while down-regulating the expression of HDAC1 and HDAC6 in RCC rats. Furthermore, the underlying mechanism of CUR in the regulation of H19 was explored, and it was revealed that CUR increased H19 expression via increasing the translational efficiency of the H19 promoter. Therefore, the treatment with CUR increased the levels of H19 and miR-675 while reducing the expression of HDAC1 and HDAC6. According to a computational analysis, HDAC1 and HDAC6 were both direct targets downstream of miR-675, and miR-675 mimics could decrease the luciferase activity of cells transfected by wild-type HDAC1 and HDAC6 3’UTR. In addition, miR-675 but not CTCF reduced the protein levels of HDAC1 and HDAC6. Nevertheless, CTCF increased the luciferase activity of cells transfected by the H19 promoter, while miR-675 mimics decreased the effect of CTCF.
Conclusions:
This study suggested that CUR could affect the prognosis of RCC by establishing a negative feedback loop of H19/miR-675/HDAC/CTCF.
The objective of this study was to explore the role of curcumin (CUR) in the control of renal cell carcinoma (RCC) as well as the molecular mechanism underlying the effect of CUR.
Material and methods:
Real-time PCR, Western blot analysis, immunohistochemistry (IHC) assay, and luciferase assay were utilized to detect the effect of CUR.
Results:
Mesoscale nanoparticles (particles) could be safely and preferentially accumulated in the kidney in a dose-dependent manner, and the specific localization of particles in the kidney reached its maximum level at a dose of 25 mg/kg. Treatment with CUR alleviated RCC by up-regulating the expression of H19 and miR-675 while down-regulating the expression of HDAC1 and HDAC6 in RCC rats. Furthermore, the underlying mechanism of CUR in the regulation of H19 was explored, and it was revealed that CUR increased H19 expression via increasing the translational efficiency of the H19 promoter. Therefore, the treatment with CUR increased the levels of H19 and miR-675 while reducing the expression of HDAC1 and HDAC6. According to a computational analysis, HDAC1 and HDAC6 were both direct targets downstream of miR-675, and miR-675 mimics could decrease the luciferase activity of cells transfected by wild-type HDAC1 and HDAC6 3’UTR. In addition, miR-675 but not CTCF reduced the protein levels of HDAC1 and HDAC6. Nevertheless, CTCF increased the luciferase activity of cells transfected by the H19 promoter, while miR-675 mimics decreased the effect of CTCF.
Conclusions:
This study suggested that CUR could affect the prognosis of RCC by establishing a negative feedback loop of H19/miR-675/HDAC/CTCF.
REFERENCES (37)
1.
Pavlović I, Pejić S, Radojević-Škodrić S, et al. The effect of antioxidant status on overall survival in renal cell carcinoma. Arch Med Sci 2020; 16: 94-101.
2.
Pei CS, Wu HY, Fan FT, Wu Y, Shen CS, Pan LQ. Influence of curcumin on HOTAIR-mediated migration of human renal cell carcinoma cells. Asian Pac J Cancer Prev 2014; 15: 4239-43.
3.
Jin H, Qiao F, Wang Y, Xu Y, Shang Y. Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway. Oncol Rep 2015; 34: 2782-9.
4.
Kasi PD, Tamilselvam R, Skalicka-Wozniak K, et al. Molecular targets of curcumin for cancer therapy: an updated review. Tumour Biol 2016; 37: 13017-28.
5.
Balasubramanian S, Eckert RL. Keratinocyte proliferation, differentiation, and apoptosis – differential mechanisms of regulation by curcumin, EGCG and apigenin. Toxicol Appl Pharmacol 2007; 224: 214-9.
7.
Yang F, Bi J, Xue X, et al. Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells. FEBS J 2012; 279: 3159-65.
8.
Liu G, Xiang T, Wu Q, Wang W. Curcumin suppresses the proliferation of gastric cancer cells by downregulating H19. Oncol Lett 2016; 12: 5156-62.
9.
Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 2013; 12: 847-65.
10.
Liz J, Portela A, Soler M, et al. Regulation of pri-miRNA processing by a long noncoding RNA transcribed from an ultraconserved region. Mol Cell 2014; 55: 138-47.
11.
He Z, Wang Y, Huang G, Wang Q, Zhao D, Chen L. The lncRNA UCA1 interacts with miR-182 to modulate glioma proliferation and migration by targeting iASPP. Arch Biochem Biophys 2017; 623-624: 1-8.
12.
Cai H, Yao J, An Y, et al. LncRNA HOTAIR acts a competing endogenous RNA to control the expression of notch3 via sponging miR-613 in pancreatic cancer. Oncotarget 2017; 8: 32905-17.
13.
He H, Wang N, Yi X, Tang C, Wang D. Long non-coding RNA H19 regulates E2F1 expression by competitively sponging endogenous miR-29a-3p in clear cell renal cell carcinoma. Cell Biosci 2017; 7: 65.
14.
Sharma NL, Groselj B, Hamdy FC, Kiltie AE. The emerging role of histone deacetylase (HDAC) inhibitors in urological cancers. BJU Int 2013; 111: 537-42.
15.
Fritzsche FR, Weichert W, Roske A, et al. Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer. BMC Cancer 2008; 8: 381.
16.
Liu G, Xiang T, Wu QF, Wang WX. Curcumin suppresses the proliferation of gastric cancer cells by downregulating H19. Oncol Lett 2016; 12: 5156-62.
17.
Liu Q, Yang B, Xie X, et al. Vigilin interacts with CCCTC-binding factor (CTCF) and is involved in CTCF-dependent regulation of the imprinted genes Igf2 and H19. FEBS J 2014; 281: 2713-25.
18.
Ulaner GA, Yang Y, Hu JF, Li T, Vu TH, Hoffman AR. CTCF binding at the insulin-like growth factor-II (IGF2)/H19 imprinting control region is insufficient to regulate IGF2/H19 expression in human tissues. Endocrinology 2003; 144: 4420-6.
19.
Manoharan H, Babcock K, Pitot HC. Changes in the DNA methylation profile of the rat H19 gene upstream region during development and transgenic hepatocarcinogenesis and its role in the imprinted transcriptional regulation of the H19 gene. Mol Carcinog 2004; 41: 1-16.
20.
Huang Y, Zheng Y, Jin C, Li X, Jia L, Li W. Long non-coding RNA H19 inhibits adipocyte differentiation of bone marrow mesenchymal stem cells through epigenetic modulation of histone deacetylases. Sci Rep 2016; 6: 28897.
21.
Hammers HJ, Verheul HM, Salumbides B, et al. Reversible epithelial to mesenchymal transition and acquired resistance to sunitinib in patients with renal cell carcinoma: evidence from a xenograft study. Mol Cancer Ther 2010; 9: 1525-35.
22.
Bar-Sela G, Epelbaum R, Schaffer M. Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications. Curr Med Chem 2010; 17: 190-7.
23.
Dhillon N, Aggarwal BB, Newman RA, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 2008; 14: 4491-9.
24.
Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer 2010; 62: 919-30.
25.
Li G, Wang Z, Chong T, Yang J, Li H, Chen H. Curcumin enhances the radiosensitivity of renal cancer cells by suppressing NF-kappaB signaling pathway. Biomed Pharmacother 2017; 94: 974-81.
26.
Zhang H, Xu W, Li B, et al. Curcumin promotes cell cycle arrest and inhibits survival of human renal cancer cells by negative modulation of the PI3K/AKT signaling pathway. Cell Biochem Biophys 2015; 73: 681-6.
27.
Seo BR, Min KJ, Cho IJ, Kim SC, Kwon TK. Curcumin significantly enhances dual PI3K/Akt and mTOR inhibitor NVP-BEZ235-induced apoptosis in human renal carcinoma Caki cells through down-regulation of p53-dependent Bcl-2 expression and inhibition of Mcl-1 protein stability. PLoS One 2014; 9: e95588.
28.
Xu S, Yang Z, Fan Y, et al. Curcumin enhances temsirolimus-induced apoptosis in human renal carcinoma cells through upregulation of YAP/p53. Oncol Lett 2016; 12: 4999-5006.
29.
Zang S, Liu T, Shi J, Qiao L. Curcumin: a promising agent targeting cancer stem cells. Anticancer Agents Med Chem 2014; 14: 787-92.
30.
Barsyte-Lovejoy D, Lau SK, Boutros PC, et al. The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer Res 2006; 66: 5330-7.
31.
Zhang EB, Han L, Yin DD, Kong R, De W, Chen J. c-Myc-induced, long, noncoding H19 affects cell proliferation and predicts a poor prognosis in patients with gastric cancer. Med Oncol 2014; 31: 914.
32.
Yan J, Zhang Y, She Q, et al. Long noncoding RNA H19/miR-675 axis promotes gastric cancer via FADD/caspase 8/caspase 3 signaling pathway. Cell Physiol Biochem 2017; 42: 2364-76.
33.
Zhou Y, Peng J, Jiang S. Role of histone acetyltransferases and histone deacetylases in adipocyte differentiation and adipogenesis. Eur J Cell Biol 2014; 93: 170-7.
34.
Yoon S, Eom GH. HDAC and HDAC inhibitor: from cancer to cardiovascular diseases. Chonnam Med J 2016; 52: 1-11.
35.
Huang Y, Zheng Y, Jia L, Li W. Long noncoding RNA H19 promotes osteoblast differentiation via TGF-beta1/Smad3/HDAC signaling pathway by deriving miR-675. Stem Cells 2015; 33: 3481-92.
36.
Kanao K, Mikami S, Mizuno R, Shinojima T, Murai M, Oya M. Decreased acetylation of histone H3 in renal cell carcinoma: a potential target of histone deacetylase inhibitors. J Urol 2008; 180: 1131-6.
37.
Jones J, Juengel E, Mickuckyte A, et al. Valproic acid blocks adhesion of renal cell carcinoma cells to endothelium and extracellular matrix. J Cell Mol Med 2009; 13: 2342-52.
Share
RELATED ARTICLE
| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
