Yonsei Med J.  2020 May;61(5):371-381. 10.3349/ymj.2020.61.5.371.

NUP210 and MicroRNA-22 Modulate Fasto Elicit HeLa Cell Cycle Arrest

• Gu Q
• Hou W
• Liu H
• Shi L
• Zhu Z
• Ye W
• Ni X

• KMID: 2500074
• DOI: http://doi.org/10.3349/ymj.2020.61.5.371

Abstract

Purpose
Cervical cancer is one of the most fatal diseases among women in under-developed countries. To improve cervical cancer treatment, discovery of new targets is needed. In this study, we investigated the expression of NUP210, miR-22, and Fas in cervical cancer tissues and their functions in cell cycle regulation.
Materials and Methods
We detected and compared the expression levels of NUP210, miR-22, and Fas in cervical cancer tissues with paired normal tissues using immunohistochemistry, Western blot, and real-time quantitative polymerase chain reaction. NUP210 was knocked down in HeLa cells via lentivirus, followed by cell cycle and proliferation analysis. Using a luciferase reporter assay, we explored the link between miR-22 and NUP210. We overexpressed miR-22 in HeLa cells and analyzed cell cycle and proliferation function. We then overexpressed miR-22 in NUP210 knockdown cells to explore the connection between Fas and miR- 22-NUP210 signaling.
Results
We found that NUP210 was overexpressed in cervical cancer patients. Knocking down NUP210 restored cell apoptosis and proliferation. We confirmed miR-22 as a regulator of NUP210 and verified that miR-22 was inhibited in cervical cancer development. We also found that restoring miR-22 expression could induce cell apoptosis. Finally, we found that miR-22-regulated expression of NUP210 could alter Fas expression and, in turn, elicit cell cycle arrest and proliferation.
Conclusion
miR-22 in cervical cancer is downregulated, resulting in NUP210 overexpression and inhibition of Fas-induced cell apoptosis.

Keyword

Cervical cancer; apoptosis; cell cycle arrest; Fas; miR-22; NUP210