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Updated: Jun 1, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

MiR-490-3p promotes cell apoptosis and cell-cycle arrest in osteosarcoma via the modulation of CDCA8/ATF3 by

Haoran Wang¹, Hanqing Wang¹, Zixiang Liu¹

¹Department of Orthopedics, Hangzhou Children's Hospital, Hangzhou, China.

Translational Pediatrics

|January 17, 2025

Abstract

Background:

Micro RNA-490-3p (miR-490-3p) is associated with a variety of malignancies. However, the role of miR-490-3p in osteosarcoma and its underlying mechanism are not yet fully understood. This study aimed to explore the role and the mechanism of miR-490-3p in osteosarcoma.

Methods:

MiR-490-3p and nucleolar and spindle-associated protein 1 (NUSAP1) expression in osteosarcoma was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), wound-healing, and transwell assays were used to detect cell proliferation, migration and invasion. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and western blot were used to evaluate the cell apoptosis. Flow cytometry was used to assess the cell cycle. In addition, luciferase reporter assay was used to confirm the binding of miR-490-3p and NUSAP1. Western blot and RT-qPCR was used to examine cell division cycle associated 8 (CDCA8) and activating transcription factor 3 (ATF3) expression.

Results:

MiR-490-3p expression was significantly decreased in the osteosarcoma cells. Following the transfection with miR-490-3p mimic, it was found that 143B cell proliferation, migration, and invasion were inhibited, while the cell apoptotic levels and cell-cycle arrest were promoted, accompanied with decreased B cell lymphoma protein-2 (Bcl-2) protein expression, and increased protein expressions of Bcl-2-associated X (Bax), cleaved caspase-3, and cleaved caspase-9. In addition, miR-490-3p was found to bind to NUSAP1, and negatively regulate NUSAP1 expression. NUSAP1 upregulation reversed the inhibitory effects of miR-490-3p overexpression on cell proliferation, migration, and invasion, and the promoting effects on cell apoptosis and cell-cycle arrest in osteosarcoma. Moreover, miR-490-3p was identified to mediate CDCA8/ATF3 by targeting NUSAP1.

Conclusions:

MiR-490-3p upregulation inhibited cell proliferation and metastasis but promoted the cell apoptosis and cell-cycle arrest in osteosarcoma via the regulation of CDCA8/ATF3 by targeting NUSAP1. Thus, miR-490-3p might be a potential therapeutic target for the treatment of osteosarcoma.

Insights

Micro RNA-490-3p (miR-490-3p) upregulation inhibits osteosarcoma cell proliferation and metastasis by targeting NUSAP1. This microRNA promotes apoptosis and cell-cycle arrest, suggesting its potential as a therapeutic target for osteosarcoma.

Area of Science:

Oncology
Molecular Biology
Biochemistry

Background:

Micro RNA-490-3p (miR-490-3p) is implicated in various cancers, but its specific role in osteosarcoma remains unclear.
Understanding the molecular mechanisms of miR-490-3p in osteosarcoma is crucial for developing targeted therapies.

Purpose of the Study:

To investigate the role of miR-490-3p in osteosarcoma.
To elucidate the underlying molecular mechanism of miR-490-3p action in osteosarcoma cells.

Main Methods:

Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were used to assess gene and protein expression.
Cell Counting Kit-8 (CCK-8), wound-healing, and transwell assays evaluated cell proliferation, migration, and invasion.
Apoptosis, cell cycle, and target gene interactions were analyzed using TUNEL assays, flow cytometry, and luciferase reporter assays.

Main Results:

miR-490-3p expression was significantly reduced in osteosarcoma tissues.
Overexpression of miR-490-3p inhibited cell proliferation, migration, and invasion while promoting apoptosis and cell-cycle arrest.
miR-490-3p directly targets Nucleolar and Spindle-Associated Protein 1 (NUSAP1), regulating its expression and subsequently affecting CDCA8/ATF3 pathways.

Conclusions:

miR-490-3p suppresses osteosarcoma progression by inhibiting proliferation and metastasis through the NUSAP1/CDCA8/ATF3 axis.
Restoration of miR-490-3p levels presents a promising therapeutic strategy for osteosarcoma treatment.

Read full analysis

Keywords:

Micro RNA-490-3p (miR-490-3p)apoptosis cell-cycle arrest nucleolar and spindle-associated protein 1 (NUSAP1)osteosarcoma

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