LINC01354 与 hnRNP-D 相互作用通过激活 Wnt/β-catenin 信号通路促进结直肠癌的增殖和转移。

LINC01354 interacting with hnRNP-D contributes to the proliferation and metastasis in colorectal cancer through activating Wnt/β-catenin signaling pathway.

机构信息

Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.

Department of Ultrasound, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510000, Guangdong Province, China.

出版信息

J Exp Clin Cancer Res. 2019 Apr 15;38(1):161. doi: 10.1186/s13046-019-1150-y.

BACKGROUND

Long non-coding RNAs (lncRNAs) have been identified to play an important role in the development and progression of various tumors, including colorectal cancer (CRC). However, the regulatory molecular mechanism by lncRNA in CRC initiation and progression has not been fully clarified.

METHODS

TCGA database was used to identify the involvement of LINC01354 in CRC. qRT-PCR and western blot were used to determine RNA and protein expression. The gain- and loss-of-function assays were conducted to explore the function of LINC01354 in the progression of CRC. In order to investigate the LINC01354-mediated mRNA in CRC tumorigenesis, we applied the profiling analysis as well as GO and KEGG analysis. Pulldown and RIP assays were applied to detect the interaction of hnRNP-D with LINC01354 and β-catenin.

RESULTS

The upregulation of LINC01354 in CRC and its prognostic significance were identified by TCGA database and confirmed in CRC tissues. Functionally, forced expression of LINC01354 promoted, while knockdown of LINC01354 inhibited cell proliferation, migration and EMT phenotype formation of CRC cells. A significant enrichment of the Wnt/β-catenin signaling pathway genes under LINC01354 overexpression. In addition, LINC01354 modulated the mRNA stability of β-catenin through interacting with hnRNP-D, thereby activating Wnt/β-catenin signaling pathway.

CONCLUSIONS

Our investigations proposed novel regulatory axis of LINC01354/hnRNP-D/Wnt/β-catenin, which might be in favor of exploring novel therapeutic regimens for the clinical treatment of CRC.

背景

长链非编码 RNA（lncRNA）已被确定在包括结直肠癌（CRC）在内的各种肿瘤的发生和发展中发挥重要作用。然而，lncRNA 在 CRC 起始和进展中的调控分子机制尚未完全阐明。

方法

TCGA 数据库用于鉴定 LINC01354 在 CRC 中的参与情况。qRT-PCR 和 Western blot 用于确定 RNA 和蛋白质表达。进行增益和缺失功能测定以探索 LINC01354 在 CRC 进展中的功能。为了研究 LINC01354 在 CRC 肿瘤发生中的介导 mRNA，我们应用了图谱分析以及 GO 和 KEGG 分析。应用下拉和 RIP 测定来检测 hnRNP-D 与 LINC01354 和 β-catenin 的相互作用。

结果

TCGA 数据库鉴定出 LINC01354 在 CRC 中的上调及其预后意义，并在 CRC 组织中得到证实。功能上，LINC01354 的强制表达促进了 CRC 细胞的增殖、迁移和 EMT 表型形成，而 LINC01354 的敲低则抑制了这些过程。在 LINC01354 过表达下，Wnt/β-catenin 信号通路基因显著富集。此外，LINC01354 通过与 hnRNP-D 相互作用调节 β-catenin 的 mRNA 稳定性，从而激活 Wnt/β-catenin 信号通路。