Biology subjects

Jame-Chenarboo, F.

Publications and source records attributed to Jame-Chenarboo, F..

3 recordsLinked to original sources

bioRxiv2024

Screening the human miRNA interactome reveals coordinated upregulation in melanoma, adding bidirectional regulation to miRNA networks.

Cellular protein expression is coordinated post-transcriptionally by an intricate regulatory network. The current presumption is that miRNA work by repression of functionally related targets within a system. In recent work, upregulation of protein expression via direct interactions of mRNA with miRNA has been found in dividing cells, providing an additional mechanism of regulation. Herein, we demonstrate coordinated upregulation of functionally-coupled proteins by miRNA. We focused on CD98hc, the heavy chain of the amino acid transporter LAT1, and -2,3-sialyltransferases ST3GAL1 and ST3GAL2, which are critical for CD98hc stability in melanoma. Profiling miRNA regulation using our high-throughput miRFluR assay, we identified miRNA that upregulated expression of both CD98hc and either ST3GAL1 or ST3GAL2. These co-upregulating miRNAs were enriched in melanoma datasets associated with transformation and progression. Our findings add co-upregulation by miRNA into miRNA regulatory networks and adds a new bidirectional twist to the impact miRNA have on protein regulation and glycosylation.

cell biology↗

bioRxiv2024

Integrated in vivo functional screens and multi-omics analyses identify alpha-2,3-sialylation as essential for melanoma maintenance

Glycosylation is a hallmark of cancer biology, and altered glycosylation influences multiple facets of melanoma growth and progression. To identify glycosyltransferases, glycans, and glycoproteins essential for melanoma maintenance, we conducted an in vivo growth screen with a pooled shRNA library of glycosyltransferases, lectin microarray profiling of benign nevi and melanoma patient samples, and mass spectrometry-based glycoproteomics. We found that -2,3 sialyltransferases ST3GAL1 and ST3GAL2 and corresponding -2,3-linked sialosides are upregulated in melanoma compared to nevi and are essential for melanoma growth in vivo and in vitro. Glycoproteomics revealed that glycoprotein targets of ST3GAL1 and ST3GAL2 are enriched in transmembrane proteins involved in growth signaling, including the amino acid transporter Solute Carrier Family 3 Member 2 (SLC3A2/CD98hc). CD98hc suppression mimicked the effect of ST3GAL1 and ST3GAL2 silencing, inhibiting melanoma cell proliferation. We found that both CD98hc protein stability and its pro-survival effect in melanoma are dependent upon -2,3 sialylation mediated by ST3GAL1 and ST3GAL2. In summary, our studies reveal that -2,3-sialosides functionally contribute to melanoma maintenance, supporting ST3GAL1 and ST3GAL2 as novel therapeutic targets in these tumors.

cancer biology↗

bioRxiv2022

miRNA upregulate protein and glycan expression via direct activation in proliferating cells

The dominant paradigm is that miRNA binding to mRNA represses protein expression. Activation by miRNA has been observed in select circumstances (quiescent cells, mitochondria), but is not thought a feature of miRNA action in actively dividing cells. Herein, we comprehensively map the miRNA regulation of -2,6-sialyltransferases ST6GAL1 and ST6GAL2 using a high-throughput assay (miRFluR). We find the majority of miRNA targeting ST6GAL1, the main enzyme controlling -2,6-sialylation, upregulate protein expression. In contrast, those that regulate ST6GAL2 are predominantly downregulatory. We provide evidence that miRNA-mediated upregulation occurs in proliferating cells and is a direct effect. Further, we show that AGO2 and FXR1 are required. Our data expands current understanding of miRNA, providing strong evidence of both upregulatory and downregulatory roles for these non-coding RNA. One-Sentence SummarymiRNA directly activate expression of -2,6-sialyltransferases and sialylation, expanding miRNA actions in dividing cells.

biochemistry↗