Journal List > J Korean Endocr Soc > v.24(1) > 1003495

Jo, Lee, Hong, Song, Shong, and Kim: Expression of miRNA 146a/b, 221 and 222 in Thyroid Cancer

Abstract

Background

miRNAs can be diagnostic markers and therapeutic targets in cancers, but few studies have been conducted in thyroid cancer. We investigated the expression levels of miRNA 146a/b, 221, and 222 which are important miRNAs in papillary thyroid cancers (PTCa), and verified their impact on clinicopathological factors.

Methods

We measured the expression of pre-miRNAs 146a/b, 221, and 222 in NPA cells treated with 10% fetal bovine serum (FBS) or in HEK293T cells transfected with RET/PTC3 or BRAFV600E expression vectors. We also investigated the relationship between miRNA expression levels in thyroid cancer tissue specimens and clinicopathological parameters.

Results

Growth stimulation with 10% FBS induced miRNA expressions in NPA cells, and transfection of RET/PTC3 and BRAFV600E also increased the expression of these miRNAs in HEK293T cells. Most (25 cases; 50%) of PTCa showed increased expression of miRNA-146a/b and 30 cases (60%) had elevated expression of miRNA-221 and miRNA-222 compared to normal thyroid samples from the contralateral lobe. However, increased miRNA expression did not correlate with clinicopathological factors.

Conclusion

Expression of miRNA 146a/b, 221, and 222 was increased by BRAFV600E and RET/PTC3 rearrangement and might have a role in tumorigenesis in PTCa. However, expression levels of these miRNAs did not correlate with clinicopathological parameters of patients with PTCa.

Figures and Tables

Fig. 1
miRNA expression in human thyroid cancer cell lines and induction of miRNA expression by serum stimulation. A. miRNA expression in human thyroid cancer cell lines. To find out the endogenous expression of miRNA-146a and miRNA-221, we performed RT-PCR targeting precursor miRNAs of these miRNAs. B. Induction of miRNA expression by serum stimulation. As we treated NPA cells with 10% fetal bovine serum, miRNA-146a/b, -221 and -222 were induced at 1 hour.
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Fig. 2
RET/PTC3 rearrangement and BRAF induced expression of miRNA-146a and miRNA-221. A. RET/PTC3 and activating mutant BRAF constructs induced tyrosine phopsphorylation and erk activation, respectively. B. RET/PTC3 rearrangement and BRAF induced expression of miRNA-146a and miRNA -221, whereas kinase-dead form of RET/PTC3 rearrangement did not.
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Fig. 3
Differential expression of miRNA in human papillary thyroid cancer. Expression levels of miRNA-146a(A), -146b(B), -221(C) and -222(D) were classified into increased or decreased group.
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Table 1
Primers for RT-PCR
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Table 2
Relationship between expression of miRNA-146a/b and clinicopathological factors
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Table 3
Relationship between expression of miRNA-221/222 and clinicopathological factors
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