Integrated Analysis of Dysregulated miRNA-gene Expression in HMGA2-silenced Retinoblastoma Cells
Nalini VenkatesanPerinkulam Ravi DeepaMadavan VasudevanVikas KhetanAshwin ReddySubramanian Krishnakumar
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Retinoblastoma
HMGA2
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The authors analyze the pathohistological archives of the Tashkent Research Institute of Ophthalmic Diseases for the years 1985-1994 and their own materials collected in recent years: 44 eyes enucleated for retinoblastoma. The microscopic picture of 44 tumors is as follows: retinoblastoma A in 12 (27.3%) cases, retinoblastoma B in 16 (36.3%), retinoblastoma C in 9 (20.4%), and mixed form in 7 (16%) cases. The total level of retinoblastoma A and B is almost 64%; this condition is positively life-threatening. The authors emphasize the necessity of health education of the population and improvement of primary health care and prophylactic check-ups of preschool children.
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In recent years, the treatment concept of retinoblastoma has changed from focusing on saving children's life to preserving the eyeballs and useful visual function. As a promising way to retain the eyeball, the application of vitrectomy in patients with retinoblastoma has long been debated. In view of the special anatomical structure of eyes and the biological characteristics of retinoblastoma cells, retinoblastoma is always prone to recurrence and metastasis after vitrectomy. Therefore, vitrectomy could hardly be a routine treatment and it should be used in retinoblastoma patients cautiously. (Chin J Ophthalmol, 2018, 54: 649-651).近年来视网膜母细胞瘤（RB）的治疗理念已从关注保护患者的生命转变为尽可能保留患者的眼球和有用视功能。玻璃体切除术作为一种保留眼球的治疗方式，是否可以应用于RB的治疗一直存在很大争议。鉴于眼球特殊的解剖结构及RB细胞的生物学特性，本文通过分析玻璃体切除术治疗RB存在的问题以及术后复发性RB的组织病理学改变，指出RB患者进行玻璃体切除术存在较高的肿瘤复发及转移风险，玻璃体切除术不宜作为RB的常规治疗方式，应审慎选择玻璃体切除术治疗RB。（中华眼科杂志，2018，54：649-651）.
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Retinoblastoma
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Of 726 eyes consecutively enucleated at the Mayo Clinic from 1954 through 1974, 41 contained retinoblastoma. In no instance was unsuspected retinoblastoma identified, nor could retinoblastoma be confirmed pathologically in an additional eight eyes in which retinoblastoma was considered in the differential diagnosis. In each of our eight misdiagnosed cases, the eyes were already blind and were cosmetically defective. The frequency of clinical misdiagnosis of retinoblastoma is high in part because it must be considered in every case of leukokoria. Although every effort was made to arrive at an accurate clinical diagnosis, the clinical misdiagnosis of retinoblastoma in a blind eye is of far less serious consequence than the clinical misdiagnosis of a tumor in a seeing eye.
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Objective To investigate the siginificance of Fas/FasL and p53 expression in retinoblastoma.Methods FasL,Fas and bcl 2 were detected immunohistochemically in 45 cases of retinoblastoma and 12 cases of normal retina.Results The expression of Fas in retinoblastoma and normal retina were very low with no difference( P 0.05).The expression of FasL in retinoblastoma and normal retina were high,but with no significantly difference( P 0.05).p53 was highly expressed in retinoblastoma and low expressed in normal retina,with significant difference( P 0.0002).Conclusion High expression of FasL and low expression of Fas in retinoblastoma and normal retina suggested that they might be associated with immune escape.The high expression of p53 in retinoblastoma was closely associated with the tumor development.\;
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Fas ligand
P53 expression
Immune escape
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Retinoblastoma protein
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Human retinoblastoma is caused by mutational inactivation of the retinoblastoma suppressor gene (RB). We have examined intraocular tumorigenicity of retinoblastoma cells in which RB expression was achieved by retroviral transduction. Retinoblastoma cells were injected into the anterior chambers of severe combined immunodeficient mouse eyes, and tumorigenicity was assessed. RB-expressing retinoblastoma cells usually failed to form progressive tumors in the anterior chamber, whereas the parental, RB-negative line, WERI-Rb27, was rapidly tumorigenic. These results support the hypothesis that inactivation of the RB gene is critical for the growth of retinoblastoma tumors. The potential use of RB reconstitution for treating human retinoblastoma is suggested by our finding that intraocular tumor growth can be suppressed by RB expression.
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Retinoblastoma protein
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To assess whether retinoblastoma formation is associated with the expression of high mobility group (HMG) A2 protein, a transcription factor that is highly expressed during embryogenesis and completely repressed in normal adult tissues, we performed Northern and Western blots and RT-PCR analyses, and immunohistochemistry to test for HMGA2 expression. We used established retinoblastoma cell lines in tumors grown in nude mice and clinical retinoblastoma specimens, and contrasted these tumors with normal embryonic and adult retina. Adenoviral-mediated antisense experiments were conducted on the retinoblastoma cell lines to suppress HMGA2 expression and determine if cell proliferation is HMGA2-dependent. We also transfected a retinoblastoma cell line to identify cis-regulatory elements and transcription initiation sites on the HMGA2 gene promoter. HMGA2 gene expression was silenced in terminally differentiated retina of 6-wk-old mice, but it was detected in retina of a 13.5-d postcoitum embryo. Reactivation of HMGA2 gene expression was observed in the retinoblastoma cell lines Y79, WERI-Rb1, and TOTL-1, in tumors derived from some of these cells propagated in nude mice, and in a high frequency of retinoblastomas excised from human patients. This suggests that expression of HMGA2 gene in retinoblastoma cells involves a derepression process. By using an antisense approach to block HMGA2 expression, we observed a decrease in the number of proliferating retinoblastoma cells. As a 1st step toward understanding HMGA2 gene reactivation in retinoblastoma, we mapped the 2 transcription initiation sites and associated positive regulatory elements within the WERI-Rb1 cells. Our discovery of derepression of HMGA2 gene expression in retinoblastoma provides the 1st evidence that this protein might contribute to neoplastic transformation of retina cells.
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HMGA2
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Eye neoplasm
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Objective To investigate the significant of Fas and bcl?2 expression in retinoblastoma.Methods The immunohistochemical staining was performed to detect Fas and bcl?2 in 45 cases of retinoblastoma and 12 cases of normal retina.Results The expression of Fas in retinoblastoma and normal retina were 0.255±0.441 and 0.083±0.289 respectively ( P =0.114?8).bcl?2 was high in retinoblastoma 2.702± 1.082 and low in normal retina 0.167±0.389,showing significant difference( P 0.000?1).Conclusion Low regulation of Fas expression in retinoblastoma and normal retina suggested that it is a throughout event which prohibit the apoptosis. The high expression of bcl?2 in retinoblastoma was close associated with the tumour development.
Retinoblastoma
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