Clinical significance of high levels of survivin and transforming growth factor beta-1 proteins in aqueous humor and serum of retinoblastoma patients

Shehata, Hanan H.; Ghalia, Azza H Abou; Khairy, Eman; Said, Azza Mohamed Ahmed; Mahmoud, Safaa S.

doi:10.1016/j.jaapos.2016.07.223

Cited by 21 publications

(23 citation statements)

References 52 publications

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“…It usually occurs in children aged <5 years, and accounts for 5% of the cases of blindness among children [4]. Multiple therapeutic options, including surgical resection, laser photocoagulation, chemotherapy, radiotherapy, and focal therapy, have undergone significant advancements in the last few decades [5]. Unfortunately, the clinical outcomes of patients with RB are still unsatisfactory, with a death rate of approximately 70% in underdeveloped and moderately developed countries [6].…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression

Dong

Wan

Yan

et al. 2020

Aging

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Long intergenic non-protein-coding RNA 324 (LINC00324) is abnormally expressed in multiple human cancer types and plays an important role in cancer initiation and progression. This study showed that LINC00324 was expressed at higher levels in retinoblastoma (RB) tumors and cell lines than in control samples. Increased LINC00324 expression closely correlated with the TNM stage, optic nerve invasion, and shorter overall survival among patients with RB. The knockdown of LINC00324 decreased RB cell proliferation, colony formation, migration, and invasion, and promoted apoptosis and cell cycle arrest in vitro as well as hindered tumor growth in vivo. With respect to the mechanism, LINC00324 acted as a competing endogenous RNA for microRNA-769-5p (miR-769-5p) in RB cells. The mRNA of signal transducer and activator of transcription 3 (STAT3) was identified as a direct target of miR-769-5p in RB cells. Rescue experiments indicated that restoration of STAT3 expression attenuated the tumor-suppressive actions of miR-769-5p in RB cells. Downregulation of miR-769-5p or restoration of STAT3 almost completely reversed the effects of LINC00324 knockdown on RB cells. Our findings describe a novel RB-related LINC00324-miR-769-5p-STAT3 axis that is implicated in the malignancy of RB in vitro and in vivo. This study may point to innovative therapeutic targets in RB.

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Section: Introductionmentioning

confidence: 99%

Long noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression

Dong

Wan

Yan

et al. 2020

Aging

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“…In recent years, enucleation has been excluded from the treatment options for RB, and different treatments are adopted according to the different stages of the tumor, aiming to retain the eyes and their functions ( 5 ). Chemoreduction, mainly systemic chemotherapy, has become the first-line approach for the clinical treatment of RB ( 6 , 7 ). It greatly improved the survival rate of the patients without affecting the structure and function of eyeballs.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑106b promotes the proliferation, migration and invasion of retinoblastoma cells by inhibiting the expression of ZBTB4 protein

Wang

Xiangrong

2018

Exp Ther Med

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The present study investigated the function of microRNA (miR)-106b in the proliferation, migration and invasion of retinoblastoma (RB) cells, and aimed to elucidate the underlying mechanism. A total of 56 patients with RB were enrolled in the present study. The expression of miR-106b in RB tissues was measured by reverse transcription quantitative polymerase chain reaction. After transfection with miR-106b mimics or miR-106b inhibitor, a Cell-Counting kit-8 assay was used to determine the proliferation of WERI-Rb-1 cells and a Transwell assay was employed to measure the migration and invasion of the cells. Western blot analysis was performed to determine the expression of zinc finger and BTB domain containing 4 (ZBTB4) protein. By silencing or overexpression of ZBTB4 protein, the biological functions of ZBTB4 in WERI-Rb-1 cells were studied. A dual luciferase reporter assay was performed to test whether ZBTB4 was a target gene of miR-106b. The expression of miR-106b in RB tissues was elevated and closely associated with the severity of the disease. Overexpression of miR-106b increased but inhibition of miR-106b expression decreased the proliferation, migration and invasion abilities of WERI-Rb-1 cells. In addition, overexpression of miR-106b decreased but inhibition of miR-106b expression increased ZBTB4 protein expression in WERI-Rb-1 cells. Similarly, overexpression of ZBTB4 reduced but inhibition of ZBTB4 expression promoted the proliferation, migration and invasion of WERI-Rb-1 cells. Finally, miR-106b regulated the expression of ZBTB4 by binding to the 3′-untranslated region of the ZBTB4 gene. The present study demonstrated that increased expression of miR-106b in RB tissues is positively associated with the metastasis and differentiation of RB cells. As an oncogene, miR-106b promotes the proliferation, migration and invasion of WERI-Rb-1 cells by inhibiting the expression of ZBTB4 protein.

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“…A total of 463 eyes with histologically confirmed Rb were included in this review, and 302 eyes in which the diagnosis of Rb was excluded were used as controls. Twelve studies examined levels of LDH in AH 21–24,31–38. Five studies examined neuron-specific enolase 26,39–42.…”

Section: Resultsmentioning

confidence: 99%

“…Five studies examined neuron-specific enolase 26,39–42. Two studies examined levels of survivin,43,24 and one of which additionally examined transforming growth factor beta (TGF-β) and LDH 24. One study examined levels of uric acid 44.…”

Section: Resultsmentioning

confidence: 99%

“…Following that initial report, further studies explored the various clinicopathological correlations associated with LDH as an AH marker of ocular disease 22,23. Over the past few decades, numerous studies have explored AH in enucleated Rb eyes and have uncovered various markers that may demonstrate clinical value for diagnosis, clinicopathological associations,22,23 monitoring response to treatment,24–26 and possibly serve as targets for therapy 27. However, because all previous studies were from enucleated eyes, clinical correlations were difficult if impossible to make and the role of the AH in management of Rb remained limited.…”

Section: Introductionmentioning

confidence: 99%

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Aqueous Humor Markers in Retinoblastoma, a Review

Ghiam

Berry

2019

Trans. Vis. Sci. Tech.

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Purpose Retinoblastoma (Rb) is the most common primary intraocular cancer in children. Unlike with most solid tumors, direct biopsy is contraindicated due to risk of tumor dissemination. However, recent therapeutic techniques have allowed for the safe extraction of aqueous humor (AH) from eyes undergoing therapy, providing the unique opportunity to use AH as a liquid biopsy for Rb. Although the extraction of AH in Rb eyes undergoing therapy is new, the consideration of whether there are tumor biomarkers in the AH is not. The current manuscript is a systematic review of all studies that have examined biomarkers in the AH of Rb eyes. The authors hypothesized that AH sampling and analysis of tumor biomarkers may have new clinical relevance for the diagnosis, prognosis, and/or management of Rb. Methods A comprehensive database search (PubMed, Web of Science, Embase, and Cochrane Databases) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to identify articles on AH markers in Rb eyes. Inclusion criteria included English language articles with original reports on AH markers in the eyes of patients with confirmed Rb. Data on marker type, number of eyes, marker means and ranges, and when available, control values and clinicopathological correlations were collected. Articles were stratified based on marker type, and assessed quantitatively and qualitatively. Results An initial database search produced 325 articles, and an additional 11 articles were identified through searching citations. After removing duplicates and applying the eligibility criteria, we selected 27 articles to be included in the current review. A total of 463 eyes with histologically confirmed Rb were included in this review. The various markers and their values, with comparison to controls and clinicopathological correlations, are discussed. Conclusions AH sampling and tumor biomarker analysis in eyes without undergoing enucleation have the potential to revolutionize the management of Rb. Translational Relevance Although previous studies evaluated markers in the AH only after enucleation and not at diagnosis or during therapy, the clinical relevance of these markers was limited. However, recent changes in the management of Rb have allowed for safe sampling of the aqueous during therapy and, thus, correlation of tumor biomarkers with disease course. Thus, the authors felt it important to revisit previous research to evaluate whether these markers may now be applicable for the diagnosis, prognosis, or management of Rb

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Clinical significance of high levels of survivin and transforming growth factor beta-1 proteins in aqueous humor and serum of retinoblastoma patients

Cited by 21 publications

References 52 publications

Long noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression

Long noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression

MicroRNA‑106b promotes the proliferation, migration and invasion of retinoblastoma cells by inhibiting the expression of ZBTB4 protein

Aqueous Humor Markers in Retinoblastoma, a Review

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