miR-130a-3p Enhances the Chemosensitivity of Y79 Retinoblastoma Cells to Vincristine by Targeting PAX6 Expression

Lu, Xiulan; Tu, Huifang; Tang, Dong-run; Huang, Xiaoming; Sun, Fenyong

doi:10.1080/02713683.2021.1984537

Cited by 5 publications

(2 citation statements)

References 41 publications

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“…A limited number of studies have shed light on the molecules responsible for conferring vincristine resistance in retinoblastoma or governing its sensitivity. Fine-tuning autophagy through CD24 and targeting PAX6 have been shown to influence retinoblastoma's responsiveness to vincristine [5,18]. Moreover, the presence of constitutively active Akt is implicated in vincristine resistance, and Akt inhibition reduces the survival of both susceptible and vincristine-resistant retinoblastoma cells by amplifying cell apoptosis and augmenting drug accumulation [19].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of vincristine sensitivity in retinoblastoma through Janus kinase inhibition by ruxolitinib

Ke,

Wang,

Zhang

et al. 2024

Anti-Cancer Drugs

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Chemotherapy remains the main approach conserving vision during the treatment of retinoblastoma, the most prevalent eye cancer in children. Unfortunately, the development of chemoresistance stands as the primary reason for treatment failure. Within this study, we showed that prolonged exposure to vincristine led to heightened expression of JAK1 and JAK2 in retinoblastoma cells, while the other members of the JAK family exhibited no such changes. Employing a genetic intervention, we demonstrated the efficacy of depleting either JAK1 or JAK2 in countering vincristine-resistant retinoblastoma cells. In addition, the dual depletion of both JAK1 and JAK2 produced a more potent inhibitory outcome compared to the depletion of either gene alone. We further demonstrated that ruxolitinib, a small molecular inhibitor of JAK1/2, effectively reduced viability and colony formation in vincristine-resistant retinoblastoma cells. It also acts synergistically with vincristine in retinoblastoma cells regardless of inherent cellular and genetic heterogeneity. The effectiveness of ruxolitinib as standalone treatment against chemoresistant retinoblastoma, as well as its combination with vincristine, was validated in multiple retinoblastoma mouse models. Importantly, mice exhibited favorable tolerance to ruxolitinib administration. We confirmed that the underlying mechanism of ruxolitinib’s action in chemoresistant retinoblastoma cells is the inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling. Our study reveals that the underlying mechanism driving ruxolitinib’s impact on chemoresistant retinoblastoma cells is the inhibition of JAK/STAT signaling. This study reveals the contribution of JAK1/2 to the development of chemoresistance in retinoblastoma and underscores the effectiveness of targeting JAK1/2 as a strategy to sensitize retinoblastoma to chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Enhancement of vincristine sensitivity in retinoblastoma through Janus kinase inhibition by ruxolitinib

Ke,

Wang,

Zhang

et al. 2024

Anti-Cancer Drugs

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“…These studies have pointed out that microRNA is closely related to the invasiveness and drug resistance of tumor cells, and regulation of microRNA can inhibit the drug resistance of tumor stem cells and improve their sensitivity to chemotherapy (5). Although some articles have studied the relationship between microRNA and RB resistance mechanism (6)(7)(8)(9), the studies are scattered, and it is not clear whether there are other signaling pathways involved in RB resistance mechanism. MiR-211-5p has been demonstrated to play an important role in several cancer types, including colorectal cancer (10), non-small cell lung cancer (11), hepatocellular carcinoma (12), and renal cell carcinoma (13).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR-211-5p Promotes Carboplatin Resistance in Human Retinoblastoma Y79 Cells by Affecting the GDNF–LIF Interaction

et al. 2022

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PurposeTo investigate the role of the miR-211-5p-GDNF signaling pathway in carboplatin resistance of retinoblastoma Y79 cells and what factors it may be affected by.MethodsA carboplatin-resistant retinoblastoma cell line (Y79R) was established in vitro. RNA-seq and microRNA-seq were constructed between Y79 and Y79R cells. RNA interference, RT-PCR, Western blot (WB), and flow cytometry were used to verify the expression of genes and proteins between the two cell lines. The TargetScan database was used to predict the microRNAs that regulate the target genes. STING sites and Co-Immunoprecipitation (COIP) were used to study protein–protein interactions.ResultsGDNF was speculated to be the top changed gene in the drug resistance in Y79R cell lines. Moreover, the speculation was verified by subsequent RT-PCR and WB results. When the expression of GDNF was knocked down, the IC50 of the Y79R cell line significantly reduced. GDNF was found to be the target gene of miR-211-5p. Downregulation of miR-211-5p promotes carboplatin resistance in human retinoblastoma Y79 cells. MiR-211-5p can regulate the expression of GDNF. Our further research also found that GDNF can bind to LIF which is also a secreted protein.ConclusionOur results suggest that downregulation of miR-211-5p promotes carboplatin resistance in human retinoblastoma Y79 cells, and this process can be affected by GDNF–LIF interaction. These results can provide evidence for the reversal of drug resistance of RB.

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Advancements in the diagnosis, prognosis, and treatment of retinoblastoma

Rajput,

Malviya,

Uniyal

2024

Canadian Journal of Ophthalmology

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miR-130a-3p Enhances the Chemosensitivity of Y79 Retinoblastoma Cells to Vincristine by Targeting PAX6 Expression

Cited by 5 publications

References 41 publications

Enhancement of vincristine sensitivity in retinoblastoma through Janus kinase inhibition by ruxolitinib

Enhancement of vincristine sensitivity in retinoblastoma through Janus kinase inhibition by ruxolitinib

Downregulation of miR-211-5p Promotes Carboplatin Resistance in Human Retinoblastoma Y79 Cells by Affecting the GDNF–LIF Interaction

Advancements in the diagnosis, prognosis, and treatment of retinoblastoma

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