Retinoblastoma Invasion Research Articles

Focused cancer pathway analysis revealed unique therapeutic targets in retinoblastoma.

Retinoblastoma (RB) is a pediatric cancer of the eye that occurs in 1/15000 live births worldwide. Albeit RB is initiated by the inactivation of RB1 gene, the disease progression relies largely on transcriptional alterations. Therefore, evaluating gene expression is vital to unveil the therapeutic targets in RB management. In this study, we employed an RT2 Profiler™ PCR array for a focused analysis of 84 cancer-specific genes in RB. An interaction network was built with gene expression data to identify the dysregulated pathways in RB. The key transcript alterations identified in 13 tumors by RT2 Profiler™ PCR array was further validated in 15 tumors by independent RT-qPCR. Out of 84 cancer-specific genes, 68 were dysregulated in RB tumors. Among the 68 genes, 23 were chosen for further analysis based on statistical significance and abundance across multiple tumors. Pathway analysis of altered genes showed the frequent perturbations of cell cycle, angiogenesis and apoptotic pathways in RB. Notably, upregulation of MCM2, MKI67, PGF, WEE1, CDC20 and downregulation of COX5A were found in all the tumors. Western blot confirmed the dysregulation of identified targets at protein levels as well. These alterations were more prominent in invasive RB, correlating with the disease pathogenesis. Our molecular analysis thus identified the potential therapeutic targets for improving retinoblastoma treatment. We also suggest that PCR array can be used as a tool for rapid and cost-effective gene expression analysis.

Ophthalmic Artery Chemosurgery for Optic Nerve Invasion in Retinoblastoma.

Ophthalmic Artery Chemosurgery for Optic Nerve Invasion in Retinoblastoma.

Identification of miR-20a as A Potential Discerning Biomarker for Non-Invasive versus Invasive Retinoblastoma.

Intraocular retinoblastoma (RB) is common in kids. Although the cause of this disease is a mutation in the RB1 gene, the formed cancerous mass in different patients is seen in non-invasive states, limited to the ocular cavity or in invasive states distributed to other parts of the body. Because this tumor's aggressiveness cannot be predicted early, these patients receive systemic chemotherapy with multiple drugs. Treating non-invasive and invasive tumors separately reduces chemical drug side effects. The aim of this study was to identify diagnostic biomarkers by separating miRNAs in blood serum from invasive and non-invasive RB patients. In this experimental study, selected three gene expression omnibus (GEO) datasets. Two were related to serum and tumor tissue miRNAs, and one was related to non-invasive and invasive RB gene expression. Examined RB gene-miRNA relationships. Then, we performed real-time polymerase chain reaction (PCR) on candidate miRNAs in the Y79 cell line and patient blood samples in non-invasive and invasive retinoblastoma. Fourteen high-expression and 7 low-expression miRNAs resulted. MiR-181, miR-135a, miR-20a, miR-373, and miR-191 were common genes with differential genes between invasive and non-invasive retinoblastoma. Only MiR-181 was upregulated in the Y79 RB cell line. Other candidate miRNAs expressed less. Invasive retinoblastomas increased serum miR-20a and miR-191. Integrated and regular bioinformatics analyses found important miRNAs in patients' and miR-20a, miR- 191, and miR-135a can distinguish non-invasive and invasive retinoblastoma, suggesting further research.

Optic nerve thickening on high-spatial-resolution MRI predicts early-stage postlaminar optic nerve invasion in retinoblastoma.

To assess the diagnostic accuracy of nerve thickening on MRI to predict early-stage postlaminar optic nerve invasion (PLONI) in retinoblastoma. Furthermore, this study aimed to incorporate measurements into a multiparametric model for radiological determination of PLONI. In this retrospective multicenter case-control study, high-spatial-resolution 3D T2-weighted MR images were used to measure the distal optic nerve. Histopathology was the reference standard for PLONI. Two neuroradiologists independently measured the optic nerve width, height, and surface at 0, 3, and 5mm from the most distal part of the optic nerve. Subsequently, PLONI was scored on contrast-enhanced T1-weighted and 3D T2-weighted images, blinded for clinical data. Optic nerve measurements with the highest diagnostic accuracy for PLONI were incorporated into a prediction model for radiological determination of PLONI. One hundred twenty-four retinoblastoma patients (median age, 22months [range, 0-113], 58 female) were included, resulting in 25 retinoblastoma eyes with histopathologically proven PLONI and 206 without PLONI. ROC analysis of axial optic nerve width measured at 0mm yielded the best area under the curve of 0.88 (95% confidence interval: 0.79, 0.96; p < 0.001). The optimal width cutoff was ≥ 2.215mm, with a sensitivity of 84% (95% CI: 64, 95%) and specificity of 83% (95% CI: 75, 89%) for detecting PLONI. Combining width measurements with the suspicion of PLONI on MRI sequences resulted in a prediction model with an improved sensitivity and specificity of respectively up to 88% and 92%. Postlaminar optic nerve thickening can predict early-stage postlaminar optic nerve invasion in retinoblastoma. This study provides an additional tool for clinicians to help determine postlaminar optic nerve invasion, which is a risk factor for developing metastatic disease in retinoblastoma patients. • The diagnostic accuracy of contrast-enhanced MRI for detecting postlaminar optic nerve invasion is limited in retinoblastoma patients. • Optic nerve thickening can predict postlaminar optic nerve invasion. • A prediction model combining MRI features has a high sensitivity and specificity for detecting postlaminar optic nerve invasion.

Identification of non-coding RNAs and their functional network associated with optic nerve invasion in retinoblastoma

Optic nerve invasion (ONI) is an important high-risk feature and prognostic indicator of retinoblastoma (RB). Emerging evidence has revealed that non-coding RNAs (ncRNAs) play important roles in tumor perineural invasion (PNI). Nevertheless, the regulatory role of ncRNAs in the ONI of RB is poorly understood. In the current study, whole-transcriptome sequencing was performed to assess the expression profiles of ncRNAs and mRNAs in RB tissues, with or without ONI. Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we predicted the biological functions of differentially expressed (DE) mRNAs. We then constructed competing endogenous RNA (ceRNA) regulatory networks based on bioinformatics analysis. The hsa_circ_0015965/lncRNA MEG3-hsa-miR-378a-5p-NOTCH1 pathway was selected and validated by real-time qPCR, western blotting, and dual luciferase reporter assays. Moreover, we demonstrated that NOTCH1 promotes the malignant progression of RB. Taken together, our results provide novel insights into the mechanism underlying optic nerve invasion in RB.

Risk of secondary tumours in patients with non-metastatic and metastatic human retinoblastoma.

Retinoblastoma is an intraocular cancer in children and infants. Despite all the available treatment options and high survival rates in children with retinoblastoma, exposure to secondary tumours in adulthood is one of the concerns that physicians face. In many cases, dysfunction of the RB1 gene is the main cause of secondary tumours due to retinoblastoma. Therefore, the aim of this study was to evaluate the incidence of other secondary tumours in children with retinoblastoma. In this regard, we performed continuous and integrated bioinformatics analyses to find genes, protein products, and signal pathways involved in other cancers. 1170 high-expression genes and 960 low-expression genes between non-invasive and invasive retinoblastoma were isolated. After examining the signal pathways, we observed bladder cancer and small cell lung cancer in the overexpressed genes. We also observed 5 cancers of endometriosis, prostate, non-small cell lung cancer, glioblastoma and renal cell carcinoma in low-expression genes. Based on the P-value index, non-small cell lung cancer, prostate and bladder cancers had the highest risk, and endometriosis cancer showed a lower probability of developing a secondary tumour in patients with retinoblastoma. In addition, the network between proteins also showed us that TP53, CDK2, SRC, MAPK1 proteins with high expression and JUN, HSP90AA1, and UBC proteins with low-expression play a significant role in candidate cancers. Lastly, we used continuous bioinformatics analysis to show that seven cancers are strongly linked to retinoblastoma cancer. Of course, more research is needed to find the best way to care for children who have been treated for retinoblastoma.

Bioinformatics Analysis and Experimental Identification of Immune-Related Genes and Immune Cells in the Progression of Retinoblastoma.

Retinoblastoma (RB) is the most common type of aggressive intraocular malignancy in children. The alteration of immunity during RB progression and invasion has not yet been well defined. This study investigated significantly altered immune-associated genes and cells related to RB invasion. The differentially expressed immune-related genes (IRGs) in noninvasive RB and invasive RB were identified by analysis of two microarray datasets (GSE97508 and GSE110811). Hub IRGs were further identified by real time PCR. The single-sample gene set enrichment analysis algorithm and Pearson correlation analysis were used to define immune cell infiltration and the relationships between hub IRGs and immune cells. Cell viability and migration were evaluated by CCK-8 and Transwell assays. A xenograft mouse model was used to verify the relationship between Src homology 3 (SH3) domain GRB2-like 2 (SH3GL2) expression and myeloid-derived suppressor cells (MDSCs). Eight upregulated genes and six downregulated IRGs were identified in invasive RB. Seven IRGs were confirmed by real-time PCR. Moreover, the proportions of MDSCs were higher in invasive RB tissues than in noninvasive RB tissues. Furthermore, correlation analysis of altered immune genes and cells suggested that SH3GL2, Langerhans cell protein 1 (LCP1) and transmembrane immune signaling adaptor TYROBP have strong connections with MDSCs. Specifically, decreased SH3GL2 expression promoted the migration of RB cells in vitro, increased the tumor size and weight, and increased the numbers of MDSCs in the tumor and spleen in vivo. This study indicated that SH3GL2 and MDSCs play a critical role in RB progression and invasion and provide candidate targets for the treatment of RB.

Cordycepin inhibited the retinoblastoma cell proliferation, migration, and invasion as well as lung metastasis via modulating c-Myc/cyclin D1 pathway.

This study aims to investigate cordycepin's effects on the proliferation, migration, and invasion of retinoblastoma (RB) cells and its regulatory mechanism. In this study, it was found that cordycepin inhibited RB cell proliferation, migration, and invasion in vitro, and pulmonary metastasis in vivo. c-Myc was a downstream target of cordycepin, and cordycepin significantly suppressed c-Myc expression, and c-Myc overexpression markedly counteracted the impacts of cordycepin on RB cell proliferation, migration, and invasion. c-Myc was positively correlated with the cell cycle pathway. Cordycepin restrained cyclin D1 expression, and c-Myc overexpression rescued this effect. In conclusion, cordycepin targets the c-Myc/cyclin D1 pathway, thereby suppressing the malignant biological behaviors of RB cells.

Long-term efficacy of enucleation combined with primary orbital implantation in children with retinoblastoma histopathological invasion of optic nerve.

ObjectiveThis study aimed to observe the long-term effect of enucleation combined with primary orbital implantation in children with histopathologic optic nerve invasive retinoblastoma (RB).MethodsWe retrospectively analyzed the clinical data and outcomes of children with RB optic nerve invasion confirmed by histopathology who underwent enucleation combined with primary orbital implantation between March 2010 and April 2014 in Beijing Tongren Hospital. The follow-up time ranged from 81 to 129 months, with a mean follow-up of 96 ± 14 months.ResultsA total of 59 children were included in this study. There were 32 males and 27 females; 52 children were affected in one eye and seven children in both eyes. The time from onset of symptoms to visit was between 3 days and 16 months, with a mean of 2.2 ± 2.8 months. The age at the of surgery was between 2 and 65 months, with an average of 24 ± 13 months. Patients were classified based on the degree of optic nerve invasion into four grades: grade 1 (invasion of prelaminar) in 28 cases, grade 2 (invasion of laminar) in 14 cases, grade 3 (invasion of retrolaminar but not reaching the optic nerve transection) in 16 cases, and grade 4 (invasion of the optic nerve transection) in 1 case. Post-operatively, all children were treated with 0–9 cycles of intravenous chemotherapy based on histopathology results from the removed eye. Of the 59 children, 13 had postoperative complications, and one died from recurrence. The survival rate was 98% (58/59). There was one case of orbital implant exposure, one of orbital cellulitis, six of enophthalmos and superior sulcus deformity, two of blepharoptosis, one of granuloma complicated with blepharoptosis, and one with a subconjunctival cyst.ConclusionFor children with RB histopathologic invasion of the optic nerve, enucleation combined with primary orbital implantation reveals future potential treatment options when combined with a full course of intravenous chemotherapy.

Retracted] Downregulation of microRNA‑198 suppresses cell proliferation and invasion in retinoblastoma by directly targeting PTEN.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the data shown for the cell invasion assays in Figs.2C and 4C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 18: 595‑602, 2018; DOI: 10.3892/mmr.2018.8979].

Retinoblastoma: A New Technique for Orbital Exenteration

Purpose and Design: Having to remove an invasive Retinoblastoma one aims to avoid an unstable orbital cover after removing the periosteum and when an usual skin graft procedure might not assure the stable support of an ocular prostheses. Methods: Based on de-doubling the lids (skin, tarsus and conjunctiva) as well as moderately freeing the peri-orbital tissues, followed by suturing together the conjunctiva of both lids, Results: purpose and design obtained. Conclusion: A reliable and stable orbital skin cover to support any prostheses Extraperiosteal orbital contents removal is considered essential to avoid a new recurrence when orbital exenteration is required. A new technique for orbital exenteration is described aiming to avoid one unstable free graft on the bare orbital bone that does not usually support the required postoperative aesthetic orbital prostheses.

Magnetic Resonance Imaging Can Reliably Differentiate Optic Nerve Inflammation from Tumor Invasion in Retinoblastoma with Orbital Cellulitis

To investigate the prevalence and magnetic resonance imaging (MRI) phenotype of retinoblastoma-associated orbital cellulitis. Additionally, this study aimed to identify postlaminar optic nerve enhancement (PLONE) patterns differentiating between inflammation and tumor invasion. A monocenter cohort study assessed the prevalence of orbital cellulitis features on MRI in retinoblastoma patients. A multicenter case-control study compared MRI features of the retinoblastoma-associated orbital cellulitis cases with retinoblastoma controls. A consecutive retinoblastoma patient cohort of 236 patients (311 eyes) was retrospectively investigated. Subsequently, 30 retinoblastoma cases with orbital cellulitis were compared with 30 matched retinoblastoma controls without cellulitis. In the cohort study, retinoblastoma MRI scans were scored on presence of inflammatory features. In the case-control study, MRI scans were scored on intraocular features and PLONE patterns. Postlaminar enhancement patterns were compared with histopathologic assessment of postlaminar tumor invasion. Interreader agreement was assessed, and exact tests with Bonferroni correction were adopted for statistical comparisons. Prevalence of retinoblastoma-associated orbital cellulitis on MRI was calculated. Frequency of intraocular MRI features was compared between cases and controls. Sensitivity and specificity of postlaminar optic nerve patterns for detection of postlaminar tumor invasion were assessed. The MRI prevalence of retinoblastoma-associated orbital cellulitis was 6.8% (16/236). Retinoblastoma with orbital cellulitis showed significantly more tumor necrosis, uveal abnormalities (inflammation, hemorrhage, and necrosis), lens luxation (all P &lt; 0.001), and a larger eye size (P= 0.012). The inflammatory pattern of optic nerve enhancement (strong enhancement similar to adjacent choroid) was solely found in orbital cellulitis cases, of which none (0/16) showed tumor invasion on histopathology. Invasive pattern enhancement was found in both cases and controls, of which 50% (5/10) showed tumor invasion on histopathology. Considering these different enhancement patterns suggestive for either inflammation or tumor invasion increased specificity for detection of postlaminar tumor invasion in orbital cellulitis cases from 32% (95% confidence interval [CI], 16-52) to 89% (95% CI, 72-98). Retinoblastoma cases presenting with orbital cellulitis show MRI findings of a larger eye size, extensive tumor necrosis, uveal abnormalities, and lens luxation. Magnetic resonance imaging contrast-enhancement patterns within the postlaminar optic nerve can differentiate between tumor invasion and inflammatory changes.

Controversies in the Management of Choroidal Invasion in Retinoblastoma.

Controversies in the Management of Choroidal Invasion in Retinoblastoma.

Investigation of Key Signaling Pathways Associating miR-204 and Common Retinopathies.

MicroRNAs are a large group of small noncoding RNAs that work in multiple cellular pathways. miR-204, as one of the key axes in the development, maintenance, and pathogenesis of the retina, plays several roles by modulating its target genes. This study was aimed at evaluating the target genes of miR-204 involved in the development and progression of common retinopathies such as glaucoma, retinoblastoma, and age-related macular degeneration. In this study, three datasets related to retinopathies (GSE50195, GSE27276, and GSE97508) were selected from Gene Expression Omnibus. miR-204 target genes were isolated from TargeScan. The shares between retinopathy and miR-204 target genes were then categorized. Using Enrichr and STRING, we highlighted the signaling pathways and the relationships between the proteins. SHC1 events in ERBB2, adherent junction's interactions, NGF signaling via TRKA from the plasma membrane, IRF3-mediated activation of type 1 IFN, pathways in upregulated genes and G0 and early G1, RORA-activated gene expression, PERK-regulated gene expression, adherent junction's interactions, and CREB phosphorylation pathways in downregulated genes were identified in glaucoma, retinoblastoma, and age-related macular degeneration. WEE1, SMC2, HMGB1, RRM2, and POLA1 proteins were also observed to be involved in the progression and invasion of retinoblastoma; SLC24A2 and DTX4 in age-related macular degeneration; and EPHB6, EFNB3, and SHC1 in glaucoma. Continuous bioinformatics analysis has shown that miR-204 has a significant presence and expression in retinal tissue, and approximately 293 genes are controlled and regulated by miR-204 in this tissue; also, target genes of miR-204 have the potential to develop various retinopathies; thus, a study of related target genes can provide appropriate treatment strategies in the future.

LncRNA CCAT1 sponges miR-218-5p to promote EMT, cellular migration and invasion of retinoblastoma by targeting MTF2

Retinoblastoma (RB) is the primary neoplasms of the retina that is most common in pediatrics age. Long non-coding RNAs (lncRNAs) has been noticed for strong relation to the occurrence and progress of retinoblastoma. Previously, we have demonstrated that lncRNA colon cancer-associated transcript 1 (CCAT1) in two RB cell lines SO-RB50 and Y79 was obviously overexpressed, and notably, lncRNA CCAT1 attenuated miR-218-5p expressionand induced proliferation, cell migration and invasion. But, how lncRNA CCAT1 acts in RB development and the potential molecular mechanisms remain to be determined. In this study, the expression levels of lncRNA CCAT1 and miR-218-5p were evaluated in RB tissues by Q-PCR, which established the results in the cell lines. Further, lncRNA CCAT1 was shown to promote epithelial-to-mesenchymal transition (EMT), cellular migration and invasion of RB cells by functional analysis of downregulation and overexpression of lncRNA CCAT1 with specific siRNA and pcDNA transfection. By performing bioinformatics and dual luciferase reporter assay, we verified the direct interaction between lncRNA CCAT1 and miR-218-5p. Besides, bioinformatics analysis indicated that metal regulatory transcription factor 2 (MTF2) might be a potent novel target for miR-218-5p, which was further validated with luciferase reporter assay, Q-PCR and also Western blot analysis. Functional analysis and rescue analysis showed that lncRNA CCAT1 via competitive binding to miR-218-5p to modulate MTF2 expression thus accelerate EMT, cell migration and invasion of RB. In conclusion, here we identified the lncRNA CCAT1/miR-218-5p/MTF2 axis in RB cell lines. Our investigations on the function of lncRNA CCAT1 and the roles of the related molecules hint a novel potential target fo RB therapy.

Extended surgical interventions in children with retinoblastoma invasion into the optic nerve

Introduction. Standard eye enucleation (EE) may not always guarantee a sufficient length of resection of the optic nerve (ON) so that the tumor cells do not spread along the optic nerve at the intersection line. Surgical access and the scope of surgical intervention are determined by the spread and localization of the tumor, as well as the qualification of the operating team.Purpose— to evaluate the role of extended surgical interventions in the spread of extraocular tumors on the ON.Materials and methods. The study included 9 patients with retinoblastoma (RB) and macroinvasion of the ON during primary magnetic resonance imaging (MRI) and/or micromorphological invasion of the ON resection line after EE. 4 of the 9 patients were treated with primary/secondary EE, induction chemotherapy (CT) and high-dose CT (HDCT), radiation therapy (RT). 5 out of 9 patients underwent secondary extended surgical interventions: exenteration of the orbit (n = 1), osteoplastic lateral orbitotomy with precanal resection of the ON (n = 2) in combination with EE in one case, subfrontal craniotomy (n = 1) and orbitozygomatic craniotomy (n = 1) with prechiasmal resection of the ON and EE with adjuvant RT (excluding the latter case) and CT, without HDCT.Results. It should be noted that the overall survival (OS) of 5 patients with complete microscopic resection (R0) after extended secondary operations was 75 ± 0.217 % with an average follow-up period of 77.25 ± 18.8 months, while in 4 patients with R1 (n = 4) without secondary extended operations with HDCT reached only 50 ± 0.25 % with an average follow-up period of 57 ± 24.8 months.Conclusion. MRI is mandatory for the primary diagnosis of RB, especially when there is a risk of the tumor spreading through the ON. Secondary surgery with R0-resection has a positive effect on survival. The need for adjuvant RT and CT after surgery should be discussed.

Exploration of retinoblastoma pathogenesis with bioinformatics.

BackgroundDifferentially expressed genes (DEGs) from retinoblastoma (RB) tissues play key roles in the progression of RB. However, the role of DEGs in different subtypes and stages of RB has not yet been systematically analyzed.MethodsIn this study, the DEGs for tumor and adjacent from 3 RB data sets GSE24673, GSE97508, and GSE110811 were analyzed with regard to the different subtypes and stages of the disease.ResultsThrough comparison with adjacent tissues, a total of 78 upregulated genes and 155 downregulated genes from the RB tissues were identified across the 3 data sets. Gene set enrichment analysis (GSEA) showed that the 3 representative genes CDK1, CDC20, and BUB1, which were all upregulated, could promote the cell cycle in RB. Compared with adjacent tissues in GSE97508, a total of 19 gigantol-targeted genes were predicted to be upregulated in invasive RB tissues. On the other hand, DEGs for tumor and adjacent from 3 RB data sets GSE24673, GSE97508, and GSE110811 were integrated with regard to invasiveness and stages of the disease, and another 19 DEGs were subsequently identified. Among these genes, UHRF1 was the only identified upregulated gene, while the other 18 were all downregulated genes. Cell Counting Kit-8 (CCK-8) experiment and GSEA results showed that UHRF1 can promote the proliferation and invasion of RB. Conversely, the downregulated representative gene CADM1 is a tumor suppressor gene, which can inhibit the progression of RB.ConclusionsThis study indicated that the verified DEGs are continuously and consistently expressed in different subtypes and stages of RB. These DEGs may be the key to understanding the development and invasion of RB.

LncRNA NEAT1 Acts as an miR-148b-3p Sponge to Regulate ROCK1 Inhibition of Retinoblastoma Growth.

BackgroundIt is reported that long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) is involved in the occurrence and development of various cancers. However, the detailed biological function and mechanism of LncRNA NEAT1 in retinoblastoma are still unclear. So we will explore the biological function and possible mechanism of LncRNA NEAT1 in retinoblastoma.Materials and MethodsQuantitative real-time PCR (qRT-PCR) was used to detect LncRNA NEAT1 in retinoblastoma tissues and cell lines. Cell counting kit 8, Transwell and flow cytometry were applied to explore cell proliferation, invasion and apoptosis. The target miRNAs (miR) of LncRNA NEAT1 and miR and downstream target genes were predicted using Starbase3.0 software and confirmed by double luciferase reporting test and RNA binding protein immunoprecipitation (RIP). Western Blot was applied to explore ROCK1 in cells, and tumor allogeneic experiment was applied to study the role of LncRNA NEAT1 on tumor growth.ResultsIt was found that LncRNA NEAT1 was up-regulated in retinoblastoma tissues, cells and serum, and the prognosis of patients with high expression of LNC RNA NEAT 1 was poor. Functional analysis showed that knocking down LncRNA NEAT1 could weaken proliferation and invasion, and accelerate apoptosis. Tumor allogeneic experiment showed that sh-NEAT1 injection can inhibit tumor growth. In addition, LncRNA NEAT1 inhibited proliferation and invasion, and promoted apoptosis through miR-148b-3p/ROCK1 axis.ConclusionLncRNA NEAT1 can mediate miR-148b-3p/ROCK1 axis to weaken the proliferation and invasion of retinoblastoma.

Long non‑coding RNA SNHG20 promotes cell proliferation, migration and invasion inretinoblastoma via the miR‑335‑5p/E2F3 axis.

Current therapies for retinoblastoma (RB) are unsatisfactory and there is an urgent need for the development of new treatment modalities. Small nucleolar RNA host gene20 (SNHG20) has been reported to serve a key oncogenic role in the development of various types of cancer, but its role in RB tumorigenesis remains to be fully determined. The present study aimed to investigate the expression patterns and biological roles of SNHG20 in RB. The expression levels of SNHG20 were measured via reverse transcription‑quantitative PCR in RB tissues and cell lines. The impact of SNHG20 status on cell proliferation, survival, migration and invasion was determined using small interfering RNA and a range of established experimental assays. The SNHG20/microRNA (miR)‑335‑5p/E2F transcription factor 3 (E2F3) signaling axis was further investigated using a dual‑luciferase activity reporter system and an RNA pull‑down assay combined with bioinformatics analyses. SNHG20 expression was significantly increased in RB tissues and cell lines. Silencing of SNHG20 in RB cells was shown to inhibit cell proliferation, clonogenic survival, migration and invasion. Moreover, mechanistic investigations demonstrated that SNHG20 could enhance the expression of E2F3 by sponging of miR‑335‑5p. These data suggested that the long non‑coding RNA SNHG20 may promote cell proliferation, migration and invasion in RB via the miR‑335‑5p/E2F3 axis.

Successful Treatment of Massive Choroidal Invasion in Retinoblastoma with Intra-arterial Chemotherapy (Ophthalmic Artery Chemosurgery)

Retinoblastoma eyes with choroidal invasion may not have to be enucleated and may be successfully managed with OAC using Melphalan, Carboplatin and Topotecan without compromising patient survival.