ArticleJournal of translational medicine2025
CircSipa1l1 modulates melanoma cell differentiation by activating the IGF2BP1-ARHGDIB axis and ERK signaling pathway.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
backgroundClinical evidence demonstrates that induction differentiation therapy is a useful treatment strategy for melanoma. Circular RNAs (circRNAs) plays a crucial role in melanoma cell proliferation, resistance and metastasis. However, the roles of circRNAs during melanoma cell differentiation have not been fully investigated. This study aimed to investigate the role and mechanism of circSipa1l1 in melanoma cell differentiation.
methodsAll-trans-retinoic acid (ATRA) or sodium phenylbutyrate-4 (PB-4) were employed to induce melanoma B16 cells differentiation, and whole transcriptome sequencing was performed to screen for differentially expressed circRNAs. RNA stability assay, quantitative real-time polymerase chain reaction (qRT-PCR), tissue microarray and fluorescence in situ hybridization (FISH) was employed to confirm the existence, expression level and subcellular localization of circSipa1l1. Cell counting kit-8 (CCK-8), colony formation, cell cycle analysis, melanin content, tyrosinase activity assay, RNA pull-down, RNA immunoprecipitation (RIP) and western blotting were used to evaluate the effect of circSipa1l1 on melanoma cell differentiation and explore its regulatory mechanism. Finally, mouse xenograft models were used to assess the effect of circSipa1l1 silencing on tumor growth in vivo.
resultsCircSipa1l1 was significantly downregulated in ATRA- or PB-4-treated B16 cells and highly expressed in melanoma patient tissues. Silencing circSipa1l1 induced cell-cycle arrest and differentiation in melanoma A375 and B16 cells, while its overexpression promoted proliferation. Mechanistically, circSipa1l1 directly interacts with insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), a key RNA-binding protein. Silencing circSipa1l1 inhibited the IGF2BP1 and rho GDP-dissociation inhibitor 2 (ARHGDIB) mRNA interaction, destabilizing ARHGDIB mRNA and subsequently inhibiting the extracellular signal-regulated kinase (ERK) signaling pathway-ultimately inducing differentiation and repressing cell cycle progression. Furthermore, silencing circSipa1l1 significantly inhibited tumor growth in both B16 and A375 xenograft models.
conclusionOur findings reveal that circSipa1l1 acts as an oncogenic circRNA by regulating the IGF2BP1/ARHGDIB/ERK axis in melanoma, suggesting it could be a potential therapeutic target for melanoma differentiation therapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.