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Published on: May 14, 2016
miR-509 inhibits cancer stemness properties in oral carcinomas via directly targeting PlK1
Ming-Yi Lu1,2, Chih-Yuan Fang3,4, Pei-Ling Hsieh5
1School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
Background/Purpose:
Oral cancer is one of the common cancers worldwide. Emerging evidence has indicated that microRNAs (non-coding RNA molecules of approximately 22 nucleotides in length) are implicated in the regulation of cancer stemness. However, the functional role of microRNA-509 (miR-509) in the characteristics of oral cancer stem cells (CSCs) has not been unraveled.
Materials And Methods:
The expression level of miR-509 in ALDH1+ and sphere oral CSCs was examined by qRT-PCR. The aldehyde dehydrogenase 1 (ALDH1) activity and CD44 expression were assessed using flow cytometry. Self-renewal, transwell migration, and colony formation assays were conducted to measure the CSC phenotypes. Besides, a luciferase reporter assay was used to confirm the direct interaction between miR-509 and its target polo-like kinase 1 (plk1).
Results:
We showed the expression of miR-509 was downregulated in the CSCs derived from oral cancer cells (SAS), and upregulation of miR-509 diminished the several CSCs features, including ALDH1 activity, self-renewal capacity, CD44 expression, migration, and colony-forming abilities. Moreover, the result from the luciferase reporter assay validated the direct binding of miR-509 to plk1.
Conclusion:
Our results suggest that the miR-509/plk1 axis may mediate the cancer stemness in oral cancer, and targeting this axis may attenuate the progression of oral cancer.
Insights
MicroRNA-509 (miR-509) is downregulated in oral cancer stem cells. Restoring miR-509 reduces cancer stemness features and may offer a therapeutic target for oral cancer.
Area of Science:
- Oncology
- Molecular Biology
- RNA Biology
Background:
- Oral cancer is a significant global health concern.
- MicroRNAs play a role in regulating cancer stemness.
- The specific function of miR-509 in oral cancer stem cells (CSCs) was previously unknown.
Purpose of the Study:
- To investigate the role of miR-509 in oral cancer stem cell characteristics.
- To determine the relationship between miR-509 and polo-like kinase 1 (plk1) in oral cancer.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure miR-509 expression.
- Flow cytometry to assess aldehyde dehydrogenase 1 (ALDH1) activity and CD44 expression.
- Functional assays (self-renewal, migration, colony formation) and luciferase reporter assay to confirm miR-509 targeting of plk1.
Main Results:
- miR-509 expression was found to be downregulated in oral CSCs.
- Upregulating miR-509 reduced CSC phenotypes, including ALDH1 activity, self-renewal, CD44 expression, migration, and colony formation.
- A direct interaction between miR-509 and its target plk1 was confirmed.
Conclusions:
- The miR-509/plk1 pathway is implicated in mediating cancer stemness in oral cancer.
- Targeting the miR-509/plk1 axis presents a potential strategy to inhibit oral cancer progression.
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