Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29126425
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Mol+Cancer
2017 ; 16
(1
): 170
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Hdac7 promotes lung tumorigenesis by inhibiting Stat3 activation
#MMPMID29126425
Lei Y
; Liu L
; Zhang S
; Guo S
; Li X
; Wang J
; Su B
; Fang Y
; Chen X
; Ke H
; Tao W
Mol Cancer
2017[Nov]; 16
(1
): 170
PMID29126425
show ga
BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. However,
the molecular mechanisms underlying lung cancer development have not been fully
understood. The functions of histone deacetylases (HDACs), a class of total
eighteen proteins (HDAC1-11 and SIRT1-7 in mammals) that deacetylate histones and
non-histone proteins, in cancers are largely unknown. METHODS: Hdac7 (+/-)/K-Ras
mice and HDAC7-depleted human lung cancer cell lines were used as models for
studying the function of Hdac7 gene in lung cancer. Kaplan-Meier survival
analysis was performed to explore the relationship between HDAC7 expression and
prognosis of human lung cancers. Recombinant lentivirus-mediated in vivo gene
expression or knockdown, Western blotting, and pull-down assay were applied to
investigate the underlying molecular mechanism by which Hdac7 promotes lung
tumorigenesis. RESULTS: The number and burden of lung tumor were dramatically
reduced in Hdac7 (+/-)/K-Ras mice compared to control K-Ras mice. Also, in Hdac7
(+/-)/K-Ras mice, cell proliferation was significantly inhibited and apoptosis in
lung tumors was greatly enhanced. Similarly, cell proliferation and
anchorage-independent growth of human lung cancer cell lines expressing shHDAC7
were also significantly suppressed and apoptosis was dramatically elevated
respectively. Mechanistic study revealed that Hdac7 mutation in mouse lung tumors
or HDAC7 depletion in human tumor cell lines resulted in significantly enhanced
acetylation and tyrosine-phosphorylation of Stat3 and HDAC7 protein directly
interacted with and deacetylateed STAT3. The Hdac7 mutant-mediated inhibitory
effects on lung tumorigenesis in mice and cell proliferation/soft agar colony
formation of human lung cancer cell lines were respectively reversed by
expressing dnStat3. Finally, the high HDAC7 mRNA level was found to be correlated
with poor prognosis of human lung cancer patients. CONCLUSION: Our study suggests
that Hdac7 promotes lung tumorigenesis by inhibiting Stat3 activation via
deacetylating Stat3 and may shed a light on the design of new therapeutic
strategies for human lung cancer.
free
free
free
