Home Blog of Signal Transduction Autophagy Autophagy Down-regulation of JMJD5 suppresses metastasis and induces apoptosis in oral squamous cell carcinoma by regulating p53/NF-κB pathway

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Down-regulation of JMJD5 suppresses metastasis and induces apoptosis in oral squamous cell carcinoma by regulating p53/NF-κB pathway

The prognosis of oral squamous cell carcinoma (OSCC) patients remains unclear, and a better understanding of the underlying molecular mechanisms is urgently required. Jumonji-C (JmjC) domain-containing protein 5 (JMJD5), renamed KDM8, has been implicated in tumorigenesis, circadian rhythm modulation, embryological development, and osteoclastogenesis. In the present study, we found that JMJD5 was over-expressed in patients with OSCC by real-time quantitative PCR (qPCR), western blot and immunohistochemical assays. When knockdown using small interfering RNA (siRNA) in OSCCs, JMJD5 was exhibited to be important for sustaining cell migration and invasion. JMJD5-knockdown increased E-cadherin expressions, and decreased N-cadherin and Vimentin expression levels in OSCC cells. Further, apoptosis was induced by JMJD5-silence through both the intrinsic and extrinsic pathways, as evidenced by the increased cleavage of Caspase-8/-9/-3 and PARP. Meanwhile, p53 expression levels were also up-regulated by JMJD5-knockdown. Suppressing p53 expressions with its inhibitor, PFTα, blocked apoptotic response in JMJD5-silenced cells. JMJD5 inhibition-induced decrease of nuclear factor-kappaB (NF-κB) was rescued by pifithrin-α (PFTα) pre-treatment. Consistently, over-expressing JMJD5 decreased p53, cleaved Caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1), whereas increased nuclear NF-κB expressions in OSCC cell lines. More importantly, targeting JMJD5 reduced xenograft tumor growth in vivo through the same molecular mechanisms evidenced in vitro. Thus, the data supplied mechanistic insights into the effects of JMJD5 on the modulation of OSCC development, illustrating that JMJD5 might be an essential prognostic indicator and therapeutic target against OSCC progression.

Related Products

Cat.No. Product Name Information
S2929 Pifithrin-α (PFTα) HBr Pifithrin-α is an inhibitor of p53, inhibiting p53-dependent transactivation of p53-responsive genes. Pifithrin-α is also a potent agonist of the aryl hydrocarbon receptor (AhR).

Related Targets

Autophagy p53