Heterogeneous Nuclear Ribonucleoprotein K Is Involved in the Estrogen-Signaling Pathway
Heterogeneous Nuclear Ribonucleoprotein K Is Involved in the Estrogen-Signaling Pathway
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异质核核糖核蛋白K参与雌激素信号途径
DOI：
10.1210/jendso/bvab048.2088
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发表时间：
2021-05-03
影响因子：
4.1
通讯作者：
Sasano H
中科院分区：
文献类型：
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作者：
Iwabuchi E;Miki Y;Ito K;Ishida T;Sasano H
异质性核核糖核蛋白K(HnRNPK)存在于细胞核、细胞质和线粒体中。它与染色质重塑、转录、剪接和翻译过程有关。尽管有报道称hnRNPK与结肠癌患者的预后不良有关，但它对胃癌有益，因为它抑制了癌细胞的增殖。HnRNPK在ER(雌激素受体)阳性/PR(孕激素受体)阳性乳腺癌中的表达高于其他亚型，但hnRNPK在ER介导的信号通路中的生物学功能尚不清楚。在本研究中，我们研究了hnRNPK在雌激素信号通路中的功能。我们初步评估了雌激素(E2)和ICI182,780作用于ERα阳性的乳腺癌细胞株MCF-7后hnRNPK的表达。这一初步评估表明，E2处理增加了hnRNPK的表达，而ICI182,780处理则降低了hnRNPK的表达。我们进一步利用siRNA研究了雌激素信号通路在hnRNPK基因敲除的MCF-7细胞中的作用，结果表明，通过E2处理，hnRNPK基因敲除降低了ERα的表达和ERα靶基因TfF1的表达。此外，我们还研究了hnRNPK和ERα之间的相互作用，因为已经报道hnRNPK与其他几种蛋白质相互作用。用免疫沉淀和邻近连接实验检测这些相互作用。然后，我们对乳腺癌和子宫内膜癌的hnRNPK进行了免疫定位。在ERα阳性的癌细胞中，HnRNPK在乳腺癌和子宫内膜癌中的表达均显著升高。相比之下，在Ki-67阳性的乳腺癌中hnRNPK的表达显著低于Ki-67阳性的乳腺癌，而在Ki-67阳性的子宫内膜癌中hnRNPK的表达显著高于Ki-67阳性的乳腺癌。人们发现hnRNPK的功能不同，这取决于它表达的癌症类型(乳腺癌或子宫内膜癌)。然而，还需要进一步的研究来阐明hnRNPK在乳腺癌和子宫内膜癌患者中的临床意义。
Heterogeneous nuclear ribonucleoprotein K (hnRNPK) has been found in the nucleus, cytoplasm, and mitochondria. It is implicated in chromatin remodeling, transcription, splicing, and translation processes. Although hnRNPK has reportedly been associated with poor prognosis in colon cancer patients, it is beneficial in gastric cancer as it inhibits cancer cell proliferation. Expression of hnRNPK in ER (Estrogen receptor) -positive/PR (Progesterone receptor) -positive breast cancer was higher than other subtypes; however, the biological functions of hnRNPK in the ER-mediated signaling pathway have not been identified. In this study, we investigated the functions of hnRNPK in the estrogen-signaling pathway. We initially evaluated hnRNPK expression upon treatment with estradiol (E2) and ICI 182,780 in ERα-positive breast cancer cell line MCF-7. This initial evaluation revealed that expression of hnRNPK was increased by E2 treatment but decreased by ICI 182,780 treatment. We further evaluated the effects of estrogen-signaling pathway in hnRNPK knockdown MCF-7 cells using siRNA, which revealed that hnRNPK knockdown decreased ERα expressions and ERα target gene TFF1 by E2 treatment. In addition, we examined the interaction between hnRNPK and ERα because hnRNPK has been reported to interact with several other proteins. These interactions were detected using immunoprecipitation and proximity ligation assay. We then immunolocalized hnRNPK in breast cancer and endometrial cancer. hnRNPK expression was significantly higher in ERα-positive cancer cells in both breast and endometrial cancers. In contrast, hnRNPK expression was significantly lower in Ki-67-positive breast cancer while being significantly higher in Ki-67-positive endometrial cancer. hnRNPK has been found to function differently, depending on the type of cancer (breast or endometrial) that it is expressed in. However, further studies are required to clarify the clinical significance of hnRNPK in breast and endometrial cancer patients.