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2017 ; 17
(1
): 477
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JMJD2A promotes the Warburg effect and nasopharyngeal carcinoma progression by
transactivating LDHA expression
#MMPMID28693517
Su Y
; Yu QH
; Wang XY
; Yu LP
; Wang ZF
; Cao YC
; Li JD
BMC Cancer
2017[Jul]; 17
(1
): 477
PMID28693517
show ga
BACKGROUND: Jumonji C domain 2A (JMJD2A), as a histone demethylases, plays a
vital role in tumorigenesis and progression. But, its functions and underlying
mechanisms of JMJD2A in nasopharyngeal carcinoma (NPC) metabolism are remained to
be clarified. In this study, we investigated glycolysis regulation by JMJD2A in
NPC and the possible mechanism. METHODS: JMJD2A expression was detected by
Western blotting and Reverse transcription quantitative real-time PCR analysis.
Then, we knocked down and ectopically expressed JMJD2A to detect changes in
glycolytic enzymes. We also evaluated the impacts of JMJD2A-lactate dehydrogenase
A (LDHA) signaling on NPC cell proliferation, migration and invasion. ChIP assays
were used to test whether JMJD2A bound to the LDHA promoter. Finally, IHC was
used to verify JMJD2A and LDHA expression in NPC tissue samples and analyze their
correlation between expression and clinical features. RESULTS: JMJD2A was
expressed at high levels in NPC tumor tissues and cell lines. Both JMJD2A and
LDHA expression were positively correlated with the tumor stage, metastasis and
clinical stage. Additionally, the level of JMJD2A was positively correlated with
LDHA expression in NPC patients, and higher JMJD2A and LDHA expression predicted
a worse prognosis. JMJD2A alteration did not influence most of glycolytic enzymes
expression, with the exception of PFK-L, PGAM-1, LDHB and LDHA, and LDHA
exhibited the greatest decrease in expression. JMJD2A silencing decreased LDHA
expression and the intracellular ATP level and increased LDH activity, lactate
production and glucose utilization, while JMJD2A overexpression produced the
opposite results. Furthermore, JMJD2A could combine to LDHA promoter region and
regulate LDHA expression at the level of transcription. Activated JMJD2A-LDHA
signaling pathway promoted NPC cell proliferation, migration and invasion.
CONCLUSIONS: JMJD2A regulated aerobic glycolysis by regulating LDHA expression.
Therefore, the novel JMJD2A-LDHA signaling pathway could contribute to the
Warburg effects in NPC progression.