J Korean Endocr Soc.  2009 Mar;24(1):17-24. 10.3803/jkes.2009.24.1.17.

Expression of miRNA 146a/b, 221 and 222 in Thyroid Cancer

Affiliations
  • 1Department of Internal Medicine, Chungnam National University Hospital, Korea.
  • 2Department of Surgery, Chungnam National University Hospital, Korea.

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.

Keyword

microRNA; prognosis; thyroid neoplasm

MeSH Terms

Cell Transformation, Neoplastic
Humans
MicroRNAs
Prognosis
Thyroid Gland
Thyroid Neoplasms
Transfection
MicroRNAs

Figure

  • 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.

  • 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.

  • 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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