Dataset Information

MicroRNA-34b-5p inhibits proliferation, stemness, migration and invasion of retinoblastoma cells via Notch signaling.

ABSTRACT: Retinoblastoma (RB) is one of the most common forms of childhood intraocular cancer. While the occurrence of RB is traditionally associated with dysregulation of the RB1 gene, efforts have been made to assess the role of several other pathways that may result in RB. The Notch signaling pathway has been identified as one of the sentinel pathways in retinal development and has been indicated to serve as a tumor suppressor. However, epigenetic modifications of the Notch signaling pathway, and their consequences on tumor establishment and progression, have received little attention. The present study attempted to elucidate the microRNA (miR)-mediated dysregulation of the Notch signaling pathway and its implications on tumor initiation. Upon recruitment of patients with RB (age, 4-25 months), the levels of miR-34b-5p were determined in tumor and adjacent healthy tissues. Simultaneously, the serum levels of miR-34b-5p were measured in tumor and healthy samples using reverse transcriptase-quantitative PCR (RT-qPCR). Binding of miR-34b-5p to Notch1 and Notch2 were confirmed bioinformatically. In vitro studies were performed in Y79 and Weri-Rb-1 RB cell lines. The cell lines were transfected with miR-34b-5p constructs and miR-34b-5p overexpression was confirmed using RT-qPCR. The impact of miR-34b-5p overexpression on cell growth and cancer stemness markers (Sox-2, Nanog, and CD133) was examined. The expression levels of Notch1 and Notch2 were evaluated in the presence of miR-34b-5p. The rescue of cell growth and cancer stemness phenotypes was evaluated by co-transfection of miR-34b-5p with Notch1 or Notch2. The results of the present study indicated that the expression levels of miR-34b-5p were reduced in patient tissues and serum samples compared with those in healthy tissues and samples. Notch1 and Notch2 expression level was negatively correlated with the expression level of miR-34b-5p. Overexpression of miR-34b-5p resulted in reduced cell proliferation, migration, invasion and cancer stemness compared with the control group. Further in vivo experiments confirmed the inhibitory effects of miR-34b-5p on RB cell proliferation. Upon co-transfection of miR-34b-5p with Notch1 or Notch2, these phenotypes were rescued with reversal of cell growth and tumor sphere formation. Collectively, the results indicated that miR-34b-5p functions as a tumor suppressor in RB via regulating the Notch signaling pathway. Therefore, miR-34b-5p may be explored for its utility as a therapeutic target in RB.

SUBMITTER: Zhang S

PROVIDER: S-EPMC7851672 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MicroRNA-34b-5p inhibits proliferation, stemness, migration and invasion of retinoblastoma cells via Notch signaling.

Zhang Shurong S Cui Zhe Z

Experimental and therapeutic medicine 20210125 3

Retinoblastoma (RB) is one of the most common forms of childhood intraocular cancer. While the occurrence of RB is traditionally associated with dysregulation of the <i>RB1</i> gene, efforts have been made to assess the role of several other pathways that may result in RB. The Notch signaling pathway has been identified as one of the sentinel pathways in retinal development and has been indicated to serve as a tumor suppressor. However, epigenetic modifications of the Notch signaling pathway, an ...[more]

PMID: 33603862

Similar Datasets

Project description:MicroRNAs (miRNAs/miRs) are highly conserved single-stranded small non-coding RNAs, which are involved in the physiological and pathological processes of breast cancer, and affect the prognosis of patients with breast cancer. The present study used the Gene Expression Omnibus (GEO)2R tool to detect miR-100 expression in breast cancer tissues obtained from GEO breast cancer-related datasets. Bioinformatics analysis revealed that miR-100 expression was downregulated in different stages, grades and lymph node metastasis stages of breast cancer, and patients with high miR-100 expression had a more favorable prognosis. Based on these analyses, Cell Counting Kit-8, wound healing and Transwell assays were performed, and the results demonstrated that overexpression of miR-100 inhibited the proliferation, migration and invasion of breast cancer cells. To verify the tumor-suppressive effect of miR-100 in breast cancer, the LinkedOmics and PITA databases were used to assess the association between miR-100 and forkhead box A1 (FOXA1). The results demonstrated that miR-100 had binding sites within the FOXA1 gene, and FOXA1 expression was negatively associated with miR-100 expression in breast cancer tissues. Similarly, a negative association was observed between miR-100 and FOXA1 expression, using the StarBase V3.0 database. The association between miR-100 and FOXA1 was further verified via reverse transcription-quantitative PCR and western blot analyses, and the dual-luciferase reporter assay. The results demonstrated that miR-100 targeted the 3'-untranslated region of FOXA1 in breast cancer cells. Furthermore, rescue experiments were performed to confirm whether miR-100 exerts its antitumor effects by regulating FOXA1. The results demonstrated that overexpression of FOXA1 promoted the proliferation, migration and invasion of breast cancer cells; thus, the antitumor effects of miR-100 in breast cancer were reversed following overexpression of FOXA1. Taken together, the results of the present study suggest that miR-100 inhibits the proliferation, migration and invasion of breast cancer cells by targeting FOXA1 expression. These results may provide a novel insight and an experimental basis for identifying effective therapeutic targets of high specificity for breast cancer.

Dataset Information

MicroRNA-34b-5p inhibits proliferation, stemness, migration and invasion of retinoblastoma cells via Notch signaling.

Publications

MicroRNA-34b-5p inhibits proliferation, stemness, migration and invasion of retinoblastoma cells via Notch signaling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets