Dataset Information

Downregulation of circ_0132266 in chronic lymphocytic leukemia promoted cell viability through miR-337-3p/PML axis.

ABSTRACT: Circular RNAs (circRNAs) have recently been reported to play crucial roles in various regulatory processes and involved in cancer onset and progression. However, the potential mechanism of circRNAs in chronic lymphocytic leukemia (CLL) remains largely unknown. Here, we observed hsa_circ_0132266 (circ_0132266), a circRNA significantly decreased in the peripheral blood mononuclear cells (PBMCs) of CLL patients compared with healthy donors, could act as an endogenous sponge of hsa-miR-337-3p (miR-337-3p) and regulate its activity, which resulted in a downstream change of target-gene PML and a consequent influence on cell viability. Taken together, our data indicated the regulatory mechanism of circ_0132266 in CLL progression through circ_0132266/miR-337-3p/PML axis, suggesting that it may serve as a biomarker as well as an exploitable therapeutic target for CLL.

SUBMITTER: Wu W

PROVIDER: S-EPMC6594798 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Downregulation of circ_0132266 in chronic lymphocytic leukemia promoted cell viability through miR-337-3p/PML axis.

Wu Wei W Wu Zijuan Z Xia Yi Y Qin Shuchao S Li Yue Y Wu Jiazhu J Liang Jinhua J Wang Li L Zhu Huayuan H Fan Lei L Fu Jianxin J Xu Wei W Jin Hui H Li Jianyong J

Aging 20190601 11

Circular RNAs (circRNAs) have recently been reported to play crucial roles in various regulatory processes and involved in cancer onset and progression. However, the potential mechanism of circRNAs in chronic lymphocytic leukemia (CLL) remains largely unknown. Here, we observed hsa_circ_0132266 (circ_0132266), a circRNA significantly decreased in the peripheral blood mononuclear cells (PBMCs) of CLL patients compared with healthy donors, could act as an endogenous sponge of hsa-miR-337-3p (miR-3 ...[more]

PMID: 31152142

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Project description:BackgroundTreating advanced colon cancer remains challenging in clinical settings because of the development of drug resistance and distant metastasis. Mechanisms underlying the metastasis of colon cancer are complex and unclear.MethodsComputational analysis was performed to determine genes associated with the exosomal long noncoding (lncRNA) plasmacytoma variant translocation 1 (PVT1)/vascular endothelial growth factor A (VEGFA) axis in patients with colon cancer. The biological importance of the exosomal lncRNA PVT1/VEGFA axis was examined in vitro by using HCT116 and LoVo cell lines and in vivo by using a patient-derived xenograft (PDX) mouse model through knockdown (by silencing of PVT1) and overexpression (by adding serum exosomes isolated from patients with distant metastasis (M-exo)).ResultsThe in silico analysis demonstrated that PVT1 overexpression was associated with poor prognosis and increased expression of metastatic markers such as VEGFA and epidermal growth factor receptor (EGFR). This finding was further validated in a small cohort of patients with colon cancer in whom increased PVT1 expression was correlated with colon cancer incidence, disease recurrence, and distant metastasis. M-exo were enriched with PVT1 and VEGFA, and both migratory and invasive abilities of colon cancer cell lines increased when they were cocultured with M-exo. The metastasis-promoting effect was accompanied by increased expression of Twist1, vimentin, and MMP2. M-exo promoted metastasis in PDX mice. In vitro silencing of PVT1 reduced colon tumorigenic properties including migratory, invasive, colony forming, and tumorsphere generation abilities. Further analysis revealed that PVT1, VEGFA, and EGFR interact with and are regulated by miR-152-3p. Increased miR-152-3p expression reduced tumorigenesis, where increased tumorigenesis was observed when miR-152-3p expression was downregulated.ConclusionExosomal PVT1 promotes colon cancer metastasis through its association with EGFR and VEGFA expression. miR-152-3p targets both PVT1 and VEGFA, and this regulatory pathway can be explored for drug development and as a prognostic biomarker.

Dataset Information

Downregulation of circ_0132266 in chronic lymphocytic leukemia promoted cell viability through miR-337-3p/PML axis.

Publications

Downregulation of circ_0132266 in chronic lymphocytic leukemia promoted cell viability through miR-337-3p/PML axis.

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