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Published on: April 25, 2018
ADAR2 Regulates Malignant Behaviour of Mesothelioma Cells Independent of RNA-editing Activity
Ken-Ichiro Sakata1, Kojiro Maeda2, Nozomi Sakurai2
1Department of Oral Diagnosis and Oral Medicine, Division of Oral Pathobiological Science, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
Background/Aim:
Malignant pleural mesothelioma (MPM) is an intractable cancer, and causes of its malignant transformation are not well known. Adenosine deaminase acting on RNA (ADAR) is an RNA-editing enzyme that converts adenosine into inosine in double-stranded RNAs potentially involved in malignant development.
Materials And Methods:
To examine the role of ADAR1 and ADAR2 in MPM, small interfering RNAs (siRNAs) against ADAR1 or ADAR2 were used.
Results:
Transfection of siRNA against ADAR2 suppressed proliferation, motility, and invasiveness of MPM cells expressing both ADAR1 and ADAR2; however, siRNA against ADAR1 did not affect these cellular activities. Overexpression of ADAR2, that was incapable of binding to RNA, suppressed growth, motility, and invasion of MPM cells. However, overexpression of ADAR2 that had no enzyme activity did not alter the malignant properties of MPM cells.
Conclusion:
Enhancement of the malignant characteristics of cultured MPM cells via ADAR2 was independent of RNA-editing activity.
Insights
Adenosine deaminase acting on RNA 2 (ADAR2) enhances malignant pleural mesothelioma (MPM) cell characteristics. This enhancement by ADAR2 is independent of its RNA-editing activity, suggesting a novel therapeutic target for this intractable cancer.
Area of Science:
- Oncology
- Molecular Biology
- RNA Biology
Background:
- Malignant pleural mesothelioma (MPM) is a challenging cancer with poorly understood causes of malignant transformation.
- Adenosine deaminase acting on RNA (ADAR) enzymes, specifically ADAR1 and ADAR2, are implicated in RNA editing and potentially in cancer development.
Purpose of the Study:
- To investigate the specific roles of ADAR1 and ADAR2 in the malignant behavior of MPM cells.
- To determine if ADAR2's impact on MPM is linked to its RNA-editing function.
Main Methods:
- Small interfering RNAs (siRNAs) targeting ADAR1 and ADAR2 were used to modulate their expression in MPM cells.
- ADAR2 variants with impaired RNA-binding and enzymatic activity were overexpressed to assess their effects.
Main Results:
- Suppression of ADAR2, but not ADAR1, using siRNAs significantly reduced MPM cell proliferation, motility, and invasiveness.
- Overexpression of a non-RNA-binding ADAR2 mutant suppressed MPM cell growth, motility, and invasion.
- Overexpression of ADAR2 lacking enzymatic activity did not alter the malignant properties of MPM cells.
Conclusions:
- ADAR2 plays a critical role in promoting the malignant characteristics of MPM cells.
- The oncogenic function of ADAR2 in MPM is independent of its RNA-editing activity, highlighting a non-canonical mechanism.
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