title: Targeting HMGA2 in Retinoblastoma Cells in vitro Using the Aptamer Strategy.
abstract: High-mobility group A2 (HMGA2) protein regulates retinoblastoma (RB) cancer cell proliferation. Here, a stable phosphorothioate-modified HMGA2 aptamer was used to block HMGA2 protein function in RB cells. HMGA2-aptamer internalisation in RB cells (Y79, Weri Rb1) and non-neoplastic human retinal cells (MIO-M1) were optimised. Aptamer induced dose-dependent cytotoxicity in RB cancer cells (0.25-1.5 µM). Increased expression ofTGFβ,SMAD4,CDH1,BAX,CASP 3,PARPmRNA and decreasedSNAI1,Bcl2mRNA levels in aptamer-treated RB cells suggests the activation of TGFβ-SMAD4-mediated apoptotic pathway. Synergistic effect with etoposide was observed in aptamer treated RB cells (p value ≤0.05). No significant toxicity was observed in non-neoplastic retinal cells.
authors.affiliation: Department of Larsen & Toubro Ocular Pathology, The Kamalnayan Bajaj Institute for Research in Vision & Ophthalmology, Vision Research Foundation, Chennai, India; Birla Institute of Technology and Science (BITS), Pilani, India.
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Nalini
authors.affiliation: Department of Biological Sciences, Birla Institute of Technology and Science (BITS), Pilani, India.
authors.forename: Perinkulam Ravi
authors.initials: PR
authors.lastname: Deepa
authors.affiliation: Department of Larsen & Toubro Ocular Pathology, The Kamalnayan Bajaj Institute for Research in Vision & Ophthalmology, Vision Research Foundation, Chennai, India.
authors.forename: Rajeswari
authors.initials: R
authors.lastname: Raguraman
authors.affiliation: Department of Vitreoretina and Oncology, Medical Research Foundation, Sankara Nethralaya, Chennai, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Khetan
authors.affiliation: Department of Ophthalmology, Barts Health NHS Trust, London, UK.
authors.forename: Maddy Ashwin
authors.initials: MA
authors.lastname: Reddy
authors.affiliation: Department of Larsen & Toubro Ocular Pathology, The Kamalnayan Bajaj Institute for Research in Vision & Ophthalmology, Vision Research Foundation, Chennai, India.
authors.forename: Subramanian
authors.initials: S
authors.lastname: Krishnakumar
keywords: Etoposide; HMGA2; HMGA2-aptamer; Retinoblastoma; TGFβ-SMAD4