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SnoRD126 通过与 hnRNPK 结合转录调控 FGFR2 激活促进肝癌细胞增殖。

SnoRD126 promotes the proliferation of hepatocellular carcinoma cells through transcriptional regulation of FGFR2 activation in combination with hnRNPK.

机构信息

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Clinical Medical Research Center of Hepatic Surgery in Hubei Province, Wuhan, China.

出版信息

Aging (Albany NY). 2021 Apr 23;13(9):13300-13317. doi: 10.18632/aging.203014.

DOI:10.18632/aging.203014
PMID:33891563
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8148486/
Abstract

Liver cancer is the sixth most common malignancy and the fourth leading cause of cancer-related death worldwide. Hepatocellular carcinoma (HCC) is the primary type of liver cancer. Small nucleolar RNA (snoRNA) dysfunctions have been associated with cancer development. SnoRD126 is an orphan C/D box snoRNA. How snoRD126 activates the PI3K-AKT pathway, and which domain of snoRD126 exerts its oncogenic function was heretofore completely unknown. Here, we demonstrate that snoRD126 binds to hnRNPK protein to regulate FGFR2 expression and activate the PI3K-AKT pathway. Importantly, we identified the critical domain of snoRD126 responsible for its cancer-promoting functions. Our study further confirms the role of snoRD126 in the progression of HCC and suggests that knockdown snoRD126 may be of potential value as a novel therapeutic approach for the treatment of HCC.

摘要

肝癌是全球第六大常见恶性肿瘤，也是癌症相关死亡的第四大主要原因。肝细胞癌 (HCC) 是肝癌的主要类型。小核仁 RNA (snoRNA) 功能障碍与癌症的发生有关。 snoRD126 是一种孤儿 C/D 盒 snoRNA。 snoRD126 如何激活 PI3K-AKT 通路，以及 snoRD126 的哪个结构域发挥其致癌功能，迄今尚完全不清楚。在这里，我们证明 snoRD126 与 hnRNPK 蛋白结合，调节 FGFR2 的表达并激活 PI3K-AKT 通路。重要的是，我们确定了 snoRD126 负责其促进癌症功能的关键结构域。我们的研究进一步证实了 snoRD126 在 HCC 进展中的作用，并表明敲低 snoRD126 可能作为 HCC 治疗的一种新的潜在治疗方法具有潜在价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bbd/8148486/84443defcb50/aging-13-203014-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bbd/8148486/5bb1b7013ce5/aging-13-203014-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bbd/8148486/84443defcb50/aging-13-203014-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bbd/8148486/16e6447a6695/aging-13-203014-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bbd/8148486/64bf848ed509/aging-13-203014-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bbd/8148486/5d6abb5e3042/aging-13-203014-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bbd/8148486/5bb1b7013ce5/aging-13-203014-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bbd/8148486/84443defcb50/aging-13-203014-g007.jpg

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