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Updated: May 8, 2026

The Lambda Select cII Mutation Detection System
Published on: April 26, 2018
miR-34a suppresses mutagenesis by inducing apoptosis in human lymphoblastoid TK6 cells
Xinrong Chen1, Yongbin Zhang, Jian Yan
1Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA.
Abstract:
miR-34a, a tumor suppressor miRNA, has been identified as a direct transcriptional target of P53. miRNA precursors and inhibitors have been used to modulate the expression of their targeted mRNA and thereby study miRNA functions. We indicated in our previous work that X-ray induces miR-34a expression in a time and dose dependent manner. The objective of this study was to elucidate the role of miR-34a in X-ray-induced mutations in human lymphoblast TK6 cells. Neither over-expression of miR-34a by lipid transfection of miR-34a precursor nor down regulation of endogenous miR-34a by miR-34a inhibitor had any effect on X-ray-induced micronucleus frequency in TK6 cells. Over-expression of miR-34a in TK6 cells significantly reduced X-ray induced mutant frequency (MF) in the Thymidine Kinase (TK) locus while suppression of endogenous miR-34a can increase the background level MF in TK6 cells. Furthermore, over-expression of miR-34a promoted and down-regulation of miR-34a inhibited background and X-ray-induced apoptosis in TK6 cells. Our study suggests miR-34a is an important negative regulator of mutagenesis and the mechanism is possibly mediated through apoptosis.
Insights
MicroRNA 34a (miR-34a) suppresses X-ray induced mutations in human cells by promoting apoptosis. Modulating miR-34a levels affects mutation rates and cell death following radiation exposure.
Area of Science:
- Molecular Biology
- Radiation Biology
- Genetics
Background:
- MicroRNA 34a (miR-34a) is a tumor suppressor and a target of P53.
- Previous studies showed X-rays increase miR-34a expression.
- The role of miR-34a in radiation-induced mutagenesis was unclear.
Purpose of the Study:
- To investigate the function of miR-34a in X-ray-induced mutations in human lymphoblast TK6 cells.
- To determine if miR-34a modulates X-ray-induced apoptosis.
Main Methods:
- TK6 cells were treated with miR-34a precursors or inhibitors.
- Cells were exposed to X-rays.
- Micronucleus frequency, mutant frequency (MF) at the Thymidine Kinase (TK) locus, and apoptosis were assessed.
Main Results:
- miR-34a modulation did not affect X-ray-induced micronucleus frequency.
- Over-expression of miR-34a reduced X-ray-induced MF in the TK locus.
- Suppression of miR-34a increased background MF and inhibited apoptosis.
- miR-34a over-expression promoted apoptosis.
Conclusions:
- miR-34a acts as a negative regulator of mutagenesis.
- The mechanism involves the modulation of apoptosis.
- miR-34a plays a significant role in cellular response to radiation-induced DNA damage.
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