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Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
Expression of noncoding vault RNA in human malignant cells and its importance in mitoxantrone resistance
Subash C B Gopinath1, Renu Wadhwa, Penmetcha K R Kumar
1RNA Processing Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba City 305-8566, Ibaraki, Japan.
Abstract:
Several noncoding RNAs do vital cellular functions, including gene regulation and cell differentiation. Previously, we reported that vault RNA (vRNA) has the ability to recognize chemotherapeutic compounds, such as mitoxantrone, based on biophysical and biochemical analyses. In the present study, we show that human glioblastoma-, leukemia-, and osteocarcinoma-derived cell lines overexpress vRNA and exhibit higher resistance toward mitoxantrone. Interestingly, when vRNA expression was suppressed by RNA interference in these cells, the resistance progressively decreased. In agreement with these findings, overexpression of vRNA-1 caused resistance to mitoxantrone. These results suggest a role of vRNA in mitoxantrone resistance in malignant cells and justify further studies on the importance and application of noncoding RNAs in cancer chemotherapeutics.
Insights
Vault RNA (vRNA) overexpression correlates with increased resistance to the chemotherapy drug mitoxantrone in cancer cells. Suppressing vRNA expression reduced this resistance, suggesting vRNA
Area of Science:
- Molecular Biology
- Cancer Research
- RNA Biology
Background:
- Noncoding RNAs (ncRNAs) play crucial roles in cellular functions like gene regulation.
- Vault RNA (vRNA) has previously demonstrated the ability to recognize chemotherapeutic compounds.
- Understanding ncRNA roles in drug resistance is vital for cancer treatment.
Purpose of the Study:
- To investigate the role of vault RNA (vRNA) in the resistance of cancer cells to mitoxantrone.
- To determine if vRNA expression levels correlate with mitoxantrone resistance in malignant cell lines.
Main Methods:
- Analysis of vRNA expression levels in human glioblastoma, leukemia, and osteosarcoma cell lines.
- RNA interference (RNAi) was used to suppress vRNA expression.
- Assessing the impact of vRNA suppression and overexpression on mitoxantrone resistance.
Main Results:
- Human glioblastoma, leukemia, and osteosarcoma cell lines overexpress vRNA.
- These cell lines exhibit increased resistance to mitoxantrone.
- Suppression of vRNA expression led to a decrease in mitoxantrone resistance.
- Overexpression of vRNA-1 specifically conferred resistance to mitoxantrone.
Conclusions:
- Vault RNA (vRNA) plays a significant role in mediating mitoxantrone resistance in malignant cells.
- These findings highlight the potential of targeting vRNA in cancer chemotherapeutics.
- Further research is warranted to explore the therapeutic applications of ncRNAs in cancer treatment.
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