IL-24 modulates the high mobility group (HMG) A1/miR222 /AKT signaling in lung cancer cells.

摘要: // Janani Panneerselvam 1, 4 , Akhil Srivastava Ranganayaki Muralidharan Qi Wang Wei Zheng 1 Lichao Zhao Alshine Chen 3, Yan D. Anupama Munshi 2, Rajagopal Ramesh 4, 5 Department of Pathology, The University Oklahoma Health Sciences Center, City, 73104, USA 2 Radiation Oncology, 3 Biostatistics and Epidemiology, Stephenson Cancer Graduate Program in Biomedical Sciences, Correspondence to: Ramesh, email: rajagopal-ramesh@ouhsc.edu Keywords: IL-24, lung cancer, HMGA1, miR222-3p, metastasis Received: April 21, 2016     Accepted: August 24, Published: September 02, 2016 ABSTRACT Interleukin (IL)-24, a novel tumor suppressor/cytokine exhibits antitumor activity against broad-spectrum human cancer cells. In recent study, we showed that IL-24 inhibited AKT However, the molecular mechanism inhibition by remains elusive. high mobility group (HMG) A1 member non-histone chromosomal proteins commonly referred to as architectural transcription factor, regulates various genes involved cell growth survival. Overexpression HMGA1 has been shown be associated with progression several cancers, including cancer. A study demonstrated activates function reducing protein phosphatase, phosphatase 2A subunit B (PPP2R2A) via oncogenic micro (mi) RNA-222. Based on this report hypothesized IL-24-mediated HMGA1/miR-222 axis. To test our hypothesis, present used H1299 line expressed exogenous when induced doxycycline (DOX). Induction expression cells markedly reduced mRNA levels. Using mechanistic approach, found miR-222-3p -5p levels, determined qRT-PCR. Associated miR-222 was marked increase PPP2R2A, concomitant decrease phosphorylated T308/S473 expression. SiRNA-mediated knockdown combination significantly greatly migration invasion compared individual treatments. Further inhibitor increased PPP2R2A Our results demonstrate for first time inhibits regulating signaling node acts an effective suppressor. Thus, therapy combining siRNA or should treatment