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Review
. 2022 Jun 24:12:916804.
doi: 10.3389/fonc.2022.916804. eCollection 2022.

The Isoforms of Estrogen Receptor Alpha and Beta in Thyroid Cancer

Zhongqin Gong  1 , Shucai Yang  2 , Minghui Wei  3 , Alexander C Vlantis  1 , Jason Y K Chan  1 , C Andrew van Hasselt  1 , Dongcai Li  4 , Xianhai Zeng  4 , Lingbin Xue  1 , Michael C F Tong  1 , George G Chen  1
Affiliations
Review

The Isoforms of Estrogen Receptor Alpha and Beta in Thyroid Cancer

Zhongqin Gong et al. Front Oncol. .

Abstract

The incidence of thyroid cancer was predominant in women, indicating that the sex hormone may have a role in thyroid cancer development. Generally, the sex hormone exerts its function by binding to the correspondent nuclear receptors. Therefore, aberrant of these receptors may be involved in the development of thyroid cancer. Estrogen receptor alpha (ERα) and beta (ERβ), two main estrogen receptors, have been reported to have an important role in the pathogenesis of thyroid cancer. When the ERα and ERβ genes undergo the alternative RNA splicing, some ERα and ERβ isoforms with incomplete functional domains may be formed. To date, several isoforms of ERα and ERβ have been identified. However, their expression and roles in thyroid cancer are far from clear. In this review, we summarized the expressions and roles of ERα and ERβ isoforms in thyroid cancer, aiming to provide the perspective of modulating the alternative RNA splicing of ERα and ERβ against thyroid cancer.

Keywords: ERα; ERβ; isoforms; splicing; thyroid cancer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Graphical Abstract
Graphical Abstract
ERα and ERβ can undergo alternative splicing, and several isoforms of ERα and Erβ have been identified. The roles of ERα and ERβ full length in thyroid cancer appear to be controversial. Moreover, the exact functions of other isoforms in thyroid cancer remain largely unknown. The red arrow indicates an increased expression, the green arrow represents a deceased expression in thyroid cancer.
Figure 1
Figure 1
The structure of ERα isoforms. (A) ERα mRNA contains 8 exons. NCBI reference sequence: NM_000125.4, transcript variant 1. (B) ERα coding region. (C) The protein structure of ERα66, ERα46, and ERα36. The difference among ERα66, ERα 46, and ERα36 is mainly located in AF1 and AF2 domains. DBD, DNA binding domain.
Figure 2
Figure 2
The structure of ERβ isoforms. (A) ERβ mRNA contains 9 exons. NCBI reference sequence: NM_001437.3, transcript variant a. (B) ERβ coding region. (C) The protein structure of ERβ1, ERβ2, ERβ3, ERβ4, ERβ5 and ERβΔ3. The difference among ERβ1, ERβ2, ERβ3, ERβ4, and ERβ5 is mainly located in the C-terminal domain. DBD, DNA binding domain.
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References

    1. Du L, Li R, Ge M, Wang Y, Li H, Chen W, et al. . Incidence and Mortality of Thyroid Cancer in China, 2008-2012. Chin J Cancer Res (2019) 31(1):144–51. doi: 10.21147/j.issn.1000-9604.2019.01.09 - DOI - PMC - PubMed
    1. Miranda-Filho A, Lortet-Tieulent J, Bray F, Cao B, Franceschi S, Vaccarella S, et al. . Thyroid Cancer Incidence Trends by Histology in 25 Countries: A Population-Based Study. Lancet Diabetes Endocrinol (2021) 9:225–34. doi: 10.1016/s2213-8587(21)00027-9 - DOI - PubMed
    1. Li M, Maso LD, Vaccarella S. Global Trends in Thyroid Cancer Incidence and the Impact of Overdiagnosis. Lancet Diabetes Endocrinol (2020) 8(6):468–70. doi: 10.1016/s2213-8587(20)30115-7 - DOI - PubMed
    1. Kim J, Gosnell JE, Roman SA. Geographic Influences in the Global Rise of Thyroid Cancer. Nat Rev Endocrinol (2020) 16(1):17–29. doi: 10.1038/s41574-019-0263-x - DOI - PubMed
    1. Ding DC, Chen W, Wang JH, Lin SZ, Sung FC. Thyroid Cancer Risk in Women With Infertility and Association With Fertility Medications in Taiwan. Cancer (2019) 125(10):1701–8. doi: 10.1002/cncr.31964 - DOI - PubMed

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