Histone Deacetylation Down-regulates the Expression of BNIP3 in Renal Cell Carcinoma

LIU Jian-bang, WANG Hai-zhou, LIU Zhen-hua. et al

Abstract

To investigate the down-regulation mechanism of（bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) expression in renal cell carcinoma (RCC). Methods RCC cell lines 786-O，ACHN and A498 were treated with different concentrations of histone deacetylase inhibitor TSA. Thereafter, the proliferation of RCC cells was determined with CCK-8 assay，cell apoptosis was observed by flow cytometry， and the expression levels of BNIP3 were determined by Q-PCR and Western blot，and the acetylation status of histone H3 in the promoter of BNIP3 was detected by ChIP. Results After the treatment with TSA，the proliferation of the three RCC cell lines was significantly inhibited (PBNIP3 mRNA (PBNIP3 promoter of both 786-O and ACHN was deacetylated，while the histone H3 in BNIP3 promoter of A498 was acetylated. Conclusion Histone deacetylation may be the important mechanism of BNIP3 silencing in RCC.

 

Keywords: Renal cell carcinoma BNIP3, Histone deacetylation, TSA ChIP 

 

Full Text:

PDF


References


CLARK PE. The role of VHL in clear-cell renal cell carcinoma and its relation to targeted therapy. Kidney Int, 2009,76(9):939-945.

RAY R, CHEN G, VANDE-VELDE C, et at. BNIP3 heterodimerizes with Bcl-2/Bcl-X ( L) and induces cell death independent of a Bcl-2 homology 3(BH3) domain at both mitochondrial and nonmitochondrial sites. J Biol Chem,2000, 275(2);1439-1448.

ZHANG H. BOSCH-MARCE M. SHI MOD A LA, et al. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem, 2008,283 ( 16) ; 10892-10903.

GUO K, SEARFOSS G,KROLIKOWSKI D. et al. Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death Differ.2001,8(4);367-376.

ERKAN M. KLEEFF J, ESPOSITO I, et al. Loss of BNIP3 expression is a late event in pancreatic cancer contributing to chemoresistance and worsened prognosis. Oncogene,2005,24 (27):4421-4432.

GUNARATNAM L, MORLEY M, FRANOVIC A, et al. Hypoxia inducible factor activates the transforming growth factor-alpha/epidermal growth factor receptor growth stimulatory pathway in VHL(— /— ) renal cell carcinoma cells. J Biol Chem,2003,278(45) :44966-44974.

MURAI M, TOYOTA M. SUZUKI H. et al. Aberrant methylation and silencing of the BN IP 3 gene in colorectal and gastric cancer. Clin Cancer Res,2005* 11(3): 1021-1027.

BACON AL, FOXS, TURLEY H. et al. Selective silencing of the hypoxia-inducible factor 1 target gene BN IP3 by histone deacetylation and methylation in colorectal cancer. Oncogene, 2007,26(1): 132-141.

PARK КС, HEO JH. JEON JY, et al. The novel histone deacetylase inhibitor, N-hydroxy-7-( 2-naphthylthio ) hepatonomide, exhibits potent antitumor activity due to cytochrome-c-release-mediated apoptosis in renal cell carcinoma cells. BMC Cancer, 2015, 15: 19 Г 2017-02-20 https;//bmccancer. biomedcentral. com/articles/10. 1186/ sl2885-014-1003-l. doi: 10. 1186/s 12885-01 1-1003-1.

SANTOS N, WENGER JB, HAVRE P, et al. Combination therapy for renal cell cancer; what are possible options,Oncology ,2011,81(3/4); 220-229.

HOFMANN WK, DE VOS S, ELASHOFF D, et al. Relation between resistance of Philadelphia-chromosome- positive acute lymphoblastic leukaemia to the tyrosine kinase inhibitor STI571 and gene-expression profiles; a gene- expression study. Lancet,2002,359(9305) :481-486.

BO AG JM, BEESLEY AH. FIRTH MJ. et al. Altered glucose metabolism in childhood pre-B acute lymphoblastic leukaemia. Leukemia,2006 .20(10): 1731-1737.

RIVENZON-SEGAL D, RUSHKIN E. POLAK-CHARCON S. et al. Glucose transporters and transport kinetics in retinoic acid-differentiated Т47D human breast cancer cells. Am J Physiol Endocrinol Metab,2000.279(3) :E508-E519. GABY AR. Adverse effects of dietary fructose. Ahern Med Rev,2005,10(4):294-306.

LIU H. HUANG D, MCARTHUR DL, et al. Fructose induces transketolase flux to promote pancreatic cancer growth. Cancer Res,2010,70( 15) ;6368-6376.

KUMAMOTO R, UTO H, ODA K, et al. Dietary fructose enhances the incidence of precancerous hepatocytes induced by administration of diethylnitrosamine in rat. Eur J Med Res, 2013, 8; 54 [2016-10-15]. http;//www. eurjmedres. com/content/18/1/54. doi:10. 1186/2047-783X-18-54.

AUNE D, CHAN DS, VIEIRA AR, et al. Dietary fructose, carbohydrates, glycemic indices and pancreatic cancer risk; a systematic review and meta-analysis of cohort studies. Ann Oncol,2012,23( 10) :2536-2546.

ZAMORA-LEON SP, GOLDE DW, CONCHA II, et al. Expression of the fructose transporter GLUTS in human breast cancer. Proc Natl Acad Sci U S A, 1996,93(5) ; 1847- 1852.

SHU R, DAVID ES, FERRARIS RP. Luminal fructose modulates fructose transport and GLUT-5 expression in small intestine of weaning rats. Am J Physiol, 1998,274(2 Pt 1); G232- G239.

CUI XL. SCHLESIER AM, FISHER EL, et al. Fructose- induced increases in neonatal rat intestinal fructose transport involve the Pl3-kinase/Akt signaling pathway. Am J Physiol Gastrointest Liver Physiol,2005,288(6) ;G1310-G1320.

BURANT CF. SAXENA M. Rapid reversible substrate regulation of fructose transporter expression in rat small intestine and kidney. Am J Physiol, 1994,267(1 Pt 1);G71- G79.


Refbacks

  • There are currently no refbacks.