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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 of TGF?, SMAD4, CDH1, BAX, CASP 3, PARP mRNA and decreased SNAI1, Bcl2 mRNA levels in aptamer-treated RB cells suggests the activation of TGF?-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.

SUBMITTER: Nalini V 

PROVIDER: S-EPMC5091129 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Targeting HMGA2 in Retinoblastoma Cells in vitro Using the Aptamer Strategy.

Nalini Venkatesan V   Deepa Perinkulam Ravi PR   Raguraman Rajeswari R   Khetan Vikas V   Reddy Maddy Ashwin MA   Krishnakumar Subramanian S  

Ocular oncology and pathology 20160702 4


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 of <i>TGFβ</i>, <i>SMAD4</i>, <i>CDH1</i>, <i>BAX</i>, <i>CASP 3</i>, <i>P  ...[more]

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