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Published on: April 3, 2018
Human OCTN2 (SLC22A5) is down-regulated in virus- and nonvirus-mediated cancer
Mariafrancesca Scalise1, Michele Galluccio, Rosita Accardi
1Department of Cell Biology, University of Calabria, Via P. Bucci 4c 87036 Arcavacata di Rende, Italy.
Abstract:
The expression of carnitine plasma membrane transporter OCTN2 was evaluated in virus and nonvirus-mediated cancer. Both OCTN2 mRNA and protein levels were reduced in keratinocytes retrotransduced with HPV16 E6 and E7 compared with the control. The OCTN2 expression was reduced also in keratinocytes retrotransduced with the sole HPV16 E6. A similar down-regulation of OCTN2 mRNA level was observed in a naturally HPV16-infected cancer cell line, CaSki, harbouring several copies of HPV16 whole genome. The mechanism of down-regulation is not related to p53 transcriptional activity because in SAOS (p53-null) cell line, the restoration of p53 expression did not rescue OCTN2 expression. The treatment of keratinocytes retrotransduced with HPV16 E6 and E7 with 5-aza-cytidine rescued the OCTN2 expression, indicating that the mechanism of down-regulation is linked to DNA methylation. Low levels of mRNA expression of OCTN2 were found also in several nonvirus-related epithelial cancer cell lines. The treatment of those cell lines with 5-aza-cytidine again rescued the expression of OCTN2 as well. These data demonstrate for the first time that the OCTN2 transporter is generally down-regulated in virus and nonvirus-mediated epithelial cancers, probably via methylation of its promoter region.
Insights
Carnitine transporter OCTN2 is downregulated in various cancers, likely due to DNA methylation. This impacts cancer cell metabolism and offers potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The carnitine transporter OCTN2 plays a role in cellular metabolism.
- Dysregulation of OCTN2 may contribute to cancer development.
- Human papillomavirus (HPV) is implicated in various epithelial cancers.
Purpose of the Study:
- To investigate OCTN2 expression in virus-mediated and non-virus-mediated epithelial cancers.
- To elucidate the mechanism behind OCTN2 downregulation in cancer.
Main Methods:
- Evaluating OCTN2 mRNA and protein levels in HPV-infected keratinocytes and cancer cell lines.
- Assessing the role of p53 in OCTN2 regulation.
- Utilizing 5-aza-cytidine treatment to investigate DNA methylation's role in OCTN2 expression.
Main Results:
- OCTN2 expression (mRNA and protein) was reduced in HPV16 E6/E7-transduced keratinocytes and HPV16-infected CaSki cells.
- OCTN2 downregulation was observed in non-virus-related epithelial cancer cell lines.
- 5-aza-cytidine treatment rescued OCTN2 expression, indicating DNA methylation as the mechanism.
- OCTN2 downregulation is independent of p53 transcriptional activity.
Conclusions:
- OCTN2 transporter is generally downregulated in both virus- and non-virus-mediated epithelial cancers.
- Promoter region DNA methylation is likely responsible for OCTN2 downregulation.
- This finding highlights OCTN2 as a potential biomarker and therapeutic target in epithelial cancers.
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