ArticleFrontiers in immunology2025
SPACA6-hosted miR-99b~125a~let-7e cluster shapes melanoma resistance by modulating mTOR-mediated immunosuppression.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
- Multiple roles of MicroRNAs in melanoma: biomarkers for diagnosis, prognosis, and treatment prediction.Frontiers in immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genomic, non-genomic, and immune alterations contribute to melanoma resistance to BRAF and MEK inhibitors. Here, we investigated the role of the SPACA6-hosted miR-99b~125a~let-7e cluster in modulating inflammatory processes and therapy resistance. We found that miR-99b, miR-125a, and let-7e were upregulated in progressing tumors from treated melanoma patients compared with untreated lesions, and in patients with short response duration compared with long-term responders. Similarly, miR-99b~125a~let-7e expression levels were high in melanoma cell lines with acquired resistance to BRAF/MEK inhibitors, showing upregulation of immunosuppressive cytokines. Combined inhibition of miR-99b, miR-125a and let-7e during drug treatment reduced proliferation of resistant cells and decreased the expression of pro-inflammatory cytokines such as CCL2, IL6, and IL8. Conversely, enforced overexpression of these miRNAs in drug sensitive cells promoted resistance and enhanced cytokine transcripts. In silico miR-99b, miR-125a and let-7e target gene analysis uncovered GNAI1, ADCY1 and NR6A1 genes in lipid metabolism pathways linked to BRAF/MEK inhibitor resistance, which converge on the activation of the mTOR signaling, and show down-regulation in resistant cells and tumors. RNA-seq and proteomic profiling of 3D cultures of patient-derived melanoma explants demonstrated that inhibition of the miR-99b~125a~let-7e cluster reprogrammed the tumor microenvironment, enhancing immune activation and suppressing mTOR signaling. Together, these findings identify the SPACA6-hosted miR-99b~125a~let-7e cluster as a regulator of BRAF/MEK inhibitor resistance through promotion of tumor survival and of an immunosuppressive microenvironment. Targeting this miRNA cluster may provide novel therapeutic opportunities to overcome drug resistance in metastatic melanoma.
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.