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Published on: November 11, 2022
Deregulation of sialidases in human normal and tumor tissues
Matilde Forcella1, Alessandra Mozzi1, Federico M Stefanini2
1Department of Biotechnologies and Biosciences, University of Milano-Bicocca, Milan, Italy.
Background:
Aberrant sialylation is a characteristic feature associated with cancer. The four types of mammalian sialidases identified to date have been shown to behave in different manners during carcinogenesis. While NEU1, NEU2 and NEU4 have been observed to oppose malignant phenotypes, the membrane-bound sialidase NEU3 was revealed to promote cancer progression.
Objectives:
With the aim of improving the knowledge about sialidases deregulation in various cancer types, we investigated the amount of NEU1, NEU3 and NEU4 transcripts in paired normal and tumor tissues from 170 patients with 11 cancer types.
Methods:
mRNA was extracted from patients' tissue specimens and retrotranscribed into cDNA, which was quantified by Real-Time PCR.
Results:
We found NEU1 and NEU3 to be up regulated, while NEU4 was down regulated in most cancer types. In particular, colorectal cancer tissues showed the highest increase in NEU3 expression. Both NEU1 and NEU3 showed a strong up-regulation in ovarian cancer.
Conclusions:
Our data show that human sialidases are expressed at different levels in healthy tissues and are strongly deregulated in tumors. Moreover, sialidases expression in our European cohort showed significant differences from Asian populations. Some of these peculiar features open potential applications of sialidases in cancer diagnosis and therapy.
Insights
Sialidase NEU3 promotes cancer progression, while NEU1 and NEU4 oppose it. This study found NEU1 and NEU3 are upregulated in most cancers, with NEU4 downregulated, offering potential diagnostic and therapeutic targets.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Aberrant sialylation is a hallmark of cancer.
- Mammalian sialidases (NEU1, NEU2, NEU3, NEU4) exhibit distinct roles in carcinogenesis.
- NEU3 promotes cancer progression, whereas NEU1, NEU2, and NEU4 counteract malignant phenotypes.
Purpose of the Study:
- To investigate the deregulation of NEU1, NEU3, and NEU4 transcripts in various cancer types.
- To enhance understanding of sialidase involvement in cancer progression.
- To analyze transcript levels in paired normal and tumor tissues from 170 patients across 11 cancer types.
Main Methods:
- mRNA extraction from patient tissue specimens.
- Retrotranscription of mRNA into cDNA.
- Quantification of cDNA using Real-Time PCR.
Main Results:
- NEU1 and NEU3 transcripts were upregulated in most cancer types studied.
- NEU4 transcripts were downregulated in the majority of cancer types.
- Colorectal and ovarian cancers showed particularly high upregulation of NEU3 and NEU1/NEU3, respectively.
Conclusions:
- Human sialidase expression is significantly altered in tumors compared to healthy tissues.
- Expression patterns of sialidases differ between European and Asian populations.
- Sialidase deregulation presents potential applications in cancer diagnosis and therapy.
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