HDAC2 enhances esophageal squamous cell carcinoma development through down-regulating microRNA-503-5p and promoting CXCL10

Abstract

Objective Although esophageal squamous cell carcinoma (ESCC)-oriented mechanism has been widely explored, the integrated action of histone deacetylase 2 (HDAC2), microRNA (miR)-503-5p and C-X-C motif chemokine 10 (CXCL10) in ESCC has not been thoroughly explored. Thus, we performed the research to study the role of HDAC2/miR-503-5p/CXCL10 axis in ESCC. Methods ESCC tissues and mucosal tissues (5 cm from cancer tissues) were collected, in which HDAC2, miR-503-5p and CXCL10 expression levels were tested. The mechanism of HDAC2, miR-503-5p and CXCL10 was interpreted. The viability, colony formation ability, apoptosis, invasion and migration abilities of ESCC cells were tested after HDAC2, miR-503-5p or CXCL10 expression was altered. Tumorigenesis in mice was observed to further verify the in vitro effects of HDAC2 and miR-503-5p. Results HDAC2 and CXCL10 were up-regulated while miR-503-5p was down-regulated in ESCC. HDAC2 bound to miR-503-5p and miR-503-5p targeted CXCL10. Silencing HDAC2 or restoring miR-503-5p depressed viability, colony-forming, invasion and migration abilities and enhanced apoptosis of ESCC cells in vitro, as well as suppressed ESCC tumorigenesis in vivo. Inhibition of miR-503-5p or elevation of CXCL10 negated HDAC2 knockout-induced effects on ESCC cells. Conclusion This work elucidates that HDAC2 knockdown retards the process of ESCC by elevating miR-503-5p and inhibiting CXCL10 expression, which may provide a guidance for ESCC management.

Aging-related features predict prognosis and immunotherapy efficacy in hepatocellular carcinoma

“…EEF1E1A is a novel LIHC prognosis predictor and associated with immune infiltration ( 59 ). A recent study showed that HDAC2 can bind to miR-503-5p and target CXCL10 , thus promoting the progression of esophageal squamous cell carcinoma ( 60 ). These hub genes were further shown to correlate positively with the PI3K/AKT/mTOR signal pathway molecules.…”

HDAC10 Inhibits Cervical Cancer Progression through Downregulating the HDAC10-microRNA-223-EPB41L3 Axis

“…These results are in accordance with the conclusions from recent studies that HDAC acts as a regulator in tumor via changing the nucleosome conformation of tumor cells. It is well acknowledged that HADC participates in cellular modulation in various cells by regulating miRNAs, for example, HDAC2 regulates miR-503-5p in esophageal squamous cell carcinoma [ 35 ], HDAC2 promotes the endothelial dysfunction induced by diabetes [ 36 , 37 ], and HDACs regulate the cellular differentiation in neurodegenerative diseases [ 38 ].…”

HDAC2 as a target for developing anti-cancer drugs

“…HDAC2 bound to the promoter sequences of miR-503–5p. and miR-503–5p suppressed the proliferation of ESCC cells both in vitro and in vivo [90] .…”

“…The inhibition of HDAC decreased CCAAT/enhancer-binding protein α mRNA expression in HCC cells by inducing miR-124–3p and miR-25 expression [89] . HDAC2 was upregulated, and miR-503–5p was down-regulated in ESCC [90] . HDAC2 bound to the promoter sequences of miR-503–5p.…”