Dataset Information

DJ-1 promotes colorectal cancer progression through activating PLAGL2/Wnt/BMP4 axis.

ABSTRACT: Metastasis remains a big barrier for the clinical treatment of colorectal cancer (CRC). Our previous proteomics analysis identified DJ-1 as a potential metastasis biomarker of CRC. In this study, we found that DJ-1 was upregulated in CRC. The levels of DJ-1 were closely correlated with the depths of invasion and predicted patient outcome. Enforced expression of DJ-1 could enhance CRC proliferation and metastasis in vitro and in vivo by stimulating Wnt-?-catenin signaling. Specifically, DJ-1-induced ?-catenin nuclear translocation stimulated TCF transcription activity, which promoted BMP4 expression for CRC cell migration and invasion, and elevated CCND1 expression for CRC cell proliferation, respectively. Furthermore, DJ-1-induced Wnt signaling activation was dependent on PLAGL2 expression. In conclusion, our study demonstrates that DJ-1 can promote CRC metastasis by activating PLAGL2-Wnt-BMP4 axis, suggesting novel therapeutic opportunities for postoperative adjuvant therapy in CRC patients.

SUBMITTER: Zhou J

PROVIDER: S-EPMC6115399 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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DJ-1 promotes colorectal cancer progression through activating PLAGL2/Wnt/BMP4 axis.

Zhou Jing J Liu Hao H Zhang Lian L Liu Xin X Zhang Chundong C Wang Yitao Y He Qing Q Zhang Ying Y Li Yi Y Chen Quanmei Q Zhang Lu L Wang Kui K Bu Youquan Y Lei Yunlong Y

Cell death & disease 20180829 9

Metastasis remains a big barrier for the clinical treatment of colorectal cancer (CRC). Our previous proteomics analysis identified DJ-1 as a potential metastasis biomarker of CRC. In this study, we found that DJ-1 was upregulated in CRC. The levels of DJ-1 were closely correlated with the depths of invasion and predicted patient outcome. Enforced expression of DJ-1 could enhance CRC proliferation and metastasis in vitro and in vivo by stimulating Wnt-β-catenin signaling. Specifically, DJ-1-indu ...[more]

PMID: 30158634

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Project description:BackgroundCircular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. In this study, we analyzed the circRNA expression profile in colorectal cancer (CRC) tissues and normal adjacent tissues by high-throughput sequencing. We focused on circRNA_0000392, a circRNA with significantly increased expression in CRCtissues, and further investigated its function in the progression of colorectal cancer.MethodsThe expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA sequencing. We verified the identified differentially expressed circRNAs in additional samples by qRT-PCR and selected circRNA_0000392 to evaluate its associations with clinicopathological features. Then, we knocked down circRNA_0000392 in CRC cells and investigated the in vitro and in vivo effects using functional experiments. Dual luciferase and RNA pull-down assays were performed to further explore the downstream potential molecular mechanisms.ResultsCircRNA_0000392 was significantly upregulated in CRC compared with normal adjacent tissues and cell lines. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, affecting the activation of the AKT-mTOR pathway in CRC cells.ConclusionsCircRNA_0000392 functions as an oncogene through the miR-193a-5p/PIK3R3/Akt axis in CRC cells, suggesting that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients.

Dataset Information

DJ-1 promotes colorectal cancer progression through activating PLAGL2/Wnt/BMP4 axis.

Publications

DJ-1 promotes colorectal cancer progression through activating PLAGL2/Wnt/BMP4 axis.

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