Histone deacetylase 9 downregulation decreases tumor growth and promotes apoptosis in non‐small cell lung cancer after melatonin treatment

Abstract

Histone deacetylase 9 functions as an oncogene in a variety of cancers, but its role on non-small cell lung cancer (NSCLC) has not been reported. Melatonin was proven to possess anticancer actions, whereas its effect on NSCLC and underlying mechanisms remains poorly understood. In this study, 337 patients with complete clinicopathologic characteristics who underwent NSCLC surgery were recruited for the study. We found that NSCLC patients with high HDAC9 expression were correlated with worse overall survival and poor prognosis. HDAC9 knockdown significantly reduced NSCLC cell growth and induced apoptosis both in vivo and in vitro. Melatonin application also markedly inhibited cell proliferation, metastasis, and invasion and promoted apoptosis in NSCLC cells. Moreover, RNA-seq, real-time quantitative polymerase chain reaction, and western blot analyses showed that melatonin treatment decreased the HDAC9 level in NSCLC cells. A mechanistic study revealed that HDAC9 knockdown further enhanced the anticancer activities of melatonin treatment, whereas HDAC9 overexpression partially reversed the melatonin's anticancer effects. Additionally, the in vivo study found melatonin exerted anti-proliferative and pro-apoptotic effects on xenograft tumors which were also strengthened by HDAC9 knockdown. These results indicated that HDAC9 downregulation mediated the anti-NSCLC actions of melatonin, and targeting HDAC9 may be the novel therapeutic strategy for NSCLC. K E Y W O R D Sapoptosis, HDAC9, melatonin, NSCLC, prognosis, proliferation 2 of 15 | MA et Al.

A novel long noncoding RNA, LOC440173, promotes the progression of esophageal squamous cell carcinoma by modulating the miR‐30d‐5p/HDAC9 axis and the epithelial–mesenchymal transition

“…34 HDAC9 also acts as an oncogene in non-small-cell lung cancer. 35 In the present study, we confirmed that HDAC9 was the direct target gene of miR-30d-5p and that LOC440173 regulated HDAC9 expression in ESCC via competitively sponging miR-30d-5p. In addition, we used rescue assays to clarify the function of the LOC440173/miR-30d-5p/HDAC9 axis in ESCC progression.…”

PGC1α activation by pterostilbene ameliorates acute doxorubicin cardiotoxicity by reducing oxidative stress via enhancing AMPK and SIRT1 cascades

“…After the different treatments on H9c2 cells for 24 h, the cell viability was detected via using the CCK-8 kit (7Sea, Shanghai, China) according to the previously described [47]. Optical density (OD) values were measured at 450 nm through the microplate reader (SpectraMax 190, Molecular Device, USA).…”

Extracellular vesicles and melatonin benefit embryonic develop by regulating reactive oxygen species and 5‐methylcytosine

“…8,9 It is involved in sleep and circadian rhythms, antioxidant activity, and immunity enhancement. 10 In addition, melatonin is regarded as a multifunctional oncostatic agent 11,12 and is potentially therapeutic for nonsmall cell lung cancer, 13 colorectal cancer, 14 Alzheimer's disease, 15 chronic kidney disease, 16 and acute ischemia-reperfusion liver injury. 17 Notably, some studies have showed that melatonin is involved in reproduction, fertility, and development.…”