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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Novel functions and targets of miR-944 in human cervical cancer cells
Hong Xie1, Linkiat Lee, Patrick Scicluna
1Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
Abstract:
Altered expression of specific microRNAs (miRNAs) has been observed in human cervical cancer. However, the biological functions of many of these miRNAs are yet to be discovered. We previously showed that miR-944 is significantly more abundant in cervical cancer tissues than their normal counterparts. In this study, we investigated the functions and targets of miR-944 in human cervical cancer cells. MiR-944 is located in the intron of the tumor protein p63 (TP63) gene, which is frequently overexpressed in cervical carcinomas. Using gain- and loss-of-function experiments in vitro, we demonstrate that miR-944 promotes cell proliferation, migration and invasion, but has no effect on apoptosis, in human cervical cancer cells. To identify the targets of miR-944, we performed photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation followed by deep sequencing. Among the candidate targets, we validated HECW2 (HECT domain ligase W2) and S100PBP (S100P binding protein) as direct targets of miR-944 using luciferase reporter assays and western blot analysis. Our findings reveal novel functions and targets of miR-944 in human cervical cancer cells, which may provide new insights of its role in cervical carcinogenesis.
Insights
MicroRNA-944 (miR-944) promotes cervical cancer cell growth and spread. This study identifies HECW2 and S100PBP as direct targets, offering new insights into cervical carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Specific microRNAs (miRNAs) show altered expression in cervical cancer, but their functions remain largely unknown.
- miR-944 is significantly upregulated in cervical cancer tissues compared to normal tissues.
- miR-944 is located within the intron of the tumor protein p63 (TP63) gene, often overexpressed in cervical carcinomas.
Purpose of the Study:
- To investigate the biological functions of miR-944 in human cervical cancer cells.
- To identify and validate direct molecular targets of miR-944.
- To elucidate the role of miR-944 in cervical carcinogenesis.
Main Methods:
- In vitro gain- and loss-of-function experiments were conducted on human cervical cancer cells.
- Photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation followed by deep sequencing were used to identify miRNA targets.
- Luciferase reporter assays and western blot analysis were employed for target validation.
Main Results:
- miR-944 significantly promotes cell proliferation, migration, and invasion in cervical cancer cells.
- miR-944 does not affect the apoptosis rate of cervical cancer cells.
- HECT domain ligase W2 (HECW2) and S100P binding protein (S100PBP) were validated as direct targets of miR-944.
Conclusions:
- miR-944 plays a crucial role in promoting key oncogenic behaviors in cervical cancer cells.
- The identification of HECW2 and S100PBP as direct targets provides mechanistic insights into miR-944's function.
- These findings contribute to understanding the role of miR-944 in cervical carcinogenesis and may suggest potential therapeutic targets.
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