Heterogeneous Nuclear Ribonucleoprotein K Is Involved in the Estrogen-Signaling Pathway

Abstract

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.