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Updated: Mar 3, 2026
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Altered miRNA expression in aniline-mediated cell cycle progression in rat spleen
Gangduo Wang1, Jianling Wang1, M Firoze Khan1
1a Department of Pathology , University of Texas Medical Branch , Galveston , TX , USA.
Abstract:
Aniline exposure is associated with toxicity to the spleen, however, early molecular events in aniline-induced cell cycle progression in the spleen remain unknown. MicroRNAs (miRNAs) have been implicated in tumor development by modulating key cell cycle regulators and controlling cell proliferation. This study was, therefore, undertaken on the expression of miRNAs, regulation of cyclins and cyclin-dependent kinases (CDKs) in an experimental condition that precedes a tumorigenic response. Male SD rats were treated with aniline (1 mmol/kg/day by gavage) for 7 days, and expression of miRNAs, cyclins and CDKs in rat spleens were analyzed. Microarray and/or qPCR analyses showed that aniline exposure led to significantly decreased miRNA expression of let-7a, miR-24, miR-34c, miR-100, miR-125b, and greatly increased miR-181a. The aberrant expression of miRNAs was associated with significantly increased protein expression of cyclins A, B1, D3 and E. Furthermore, remarkably enhanced expression of CDKs like CDK1, CDK2, CDK4, CDK6, especially p-CDK1 and p-CDK2 as well as alternations in the expression of pRB, p27, and CDC25A in the spleens of aniline-treated rats was also observed. The data suggest that aniline exposure leads to aberrant expression of miRNAs in the spleen which could be important in the regulation of cell cycle proteins. Our findings, thus, provide new insight into the role of miRNAs in cell cycle progression, which may contribute to aniline-induced tumorigenic response in the spleen.
Insights
Aniline exposure alters spleen microRNA (miRNA) expression, affecting cell cycle regulators like cyclins and cyclin-dependent kinases (CDKs). These molecular changes may precede spleen tumor development.
Area of Science:
- Toxicology
- Molecular Biology
- Cancer Research
Background:
- Aniline exposure is linked to spleen toxicity.
- Early molecular events in aniline-induced spleen cell cycle progression are unknown.
- MicroRNAs (miRNAs) regulate cell cycle and proliferation, potentially influencing tumor development.
Purpose of the Study:
- To investigate miRNA expression and its regulation of cyclins and cyclin-dependent kinases (CDKs) in rat spleens following aniline exposure.
- To understand molecular events preceding aniline-induced tumorigenesis in the spleen.
Main Methods:
- Male Sprague-Dawley rats were gavaged with aniline (1 mmol/kg/day) for 7 days.
- Microarray and quantitative PCR (qPCR) were used to analyze miRNA expression.
- Protein expression of cyclins, CDKs, and related cell cycle regulators was assessed.
Main Results:
- Aniline exposure significantly decreased let-7a, miR-24, miR-34c, miR-100, and miR-125b expression.
- Aniline exposure significantly increased miR-181a expression.
- Aberrant miRNA expression correlated with increased protein levels of cyclins (A, B1, D3, E) and CDKs (CDK1, CDK2, CDK4, CDK6), particularly phosphorylated forms (p-CDK1, p-CDK2), and altered pRB, p27, and CDC25A expression.
Conclusions:
- Aniline exposure induces aberrant miRNA expression in the spleen.
- These miRNA changes are associated with altered expression of key cell cycle regulatory proteins.
- The findings offer new insights into the role of miRNAs in cell cycle progression and potential contribution to aniline-induced spleen tumorigenesis.
