Long Non-Coding RNA CRNDE Regulates Angiogenesis in Hepatoblastoma by Targeting the MiR-203/VEGFA Axis

Abstract

Objective: has been shown to participate in multiple malignancies, but the role of miR-203 in hepatoblastoma (HB) remains unclear. The aim of our study was to investigate the effects of miR-203 in HB. Methods: A total of 15 pairs of HB tissues and para-tumour normal tissues were collected for the experiments. RT-qPCR and Western blotting were performed to detect the expression of CRNDE, miR-203, and VEGFA at the mRNA and/or protein levels, respectively. A dual luciferase assay verified the target relationship between miR-203 and the 3′UTR of VEGFA as well as miR-203 and CRNDE. In addition, MTT, wound healing, and tube formation assays were performed to assess the effects of miR-203, VEGFA, and CRNDE on cell proliferation, migration, and angiogenesis, respectively. Results: Our data revealed that miR-203 expression was decreased in HB tissues, while long non-coding RNA (lncRNA) CRNDE expression was increased. The dysregulation of miR-203 and CRNDE was closely related to tumour size and stage. Moreover, overexpression of miR-203 inhibited angiogenesis. A dual luciferase assay verified that VEGFA is a direct target of miR-203 and that CRNDE binds to miR-203. Furthermore, our results showed that miR-203 suppressed cell viability, migration, and angiogenesis by regulating VEGFA expression. Additionally, it was confirmed that CRNDE promoted angiogenesis by negatively regulating miR-203 expression. Conclusion: lncRNA CRNDE targets the miR-203/VEGFA axis and promotes angiogenesis in HB. These results provide insight into the underlying mechanisms of HB and indicate that CRNDE and miR-203 might be potential targets for HB therapy.

Involvement of Long Non-Coding RNAs (lncRNAs) in Tumor Angiogenesis

“…Likewise, angiogenic lncRNA MALAT-1 and highly upregulated in liver cancer (HULC) induce hepatic angiogenesis by sponging miRNAs as well. Additionally, less common lncRNAs such as Colorectal Neoplasia Differentially Expressed (CRNDE) [61], Opa interacting protein 5-antisense RNA 1 (OIP5-AS1) [62], and LINC00488 [63] are also known to induce liver cancer angiogenesis by functioning as ceRNA. In the following section, angiogenic lncRNAs are summarized by their regulatory mechanisms occurring in different tumor types.…”

“…In hepatoblastoma (HB), another type of liver cancer, the highly expressed lncRNAs CRNDE and TUG1 were shown to bind miR-203 and miR-34-5p, respectively. By acting as a ceRNA, these lncRNAs prevent the suppressive miRNA function on the target gene VEGF [52,61]. Therefore, lncRNA TUG1 might be responsible for the hypervascularity, which is characteristic for hepatoblastoma [52].…”

High Expression of ROMO1 Aggravates the Malignancy of Hepatoblastoma

“…For example, microRNA-26-5p functioned as a new inhibitor of HB by repressing the LIN28B-RAN-AURKA pathway [ 7 ]. LncRNA CRNDE promoted the angiogenesis of HB by regulating the miR-203/VEGFA axis [ 8 ]. Circ-STAT3 promoted HB progression through acting as a sponge for miR-29a/b/c-3p [ 9 ].…”

Long Non-coding RNA CRNDE Exacerbates NPC Advancement Mediated by the miR-545-5p/CCND2 Axis

“…Previous literature demonstrated miR-545-5p to be downregulated within colon adenocarcinoma and contributes to its proliferative, apoptotic, migrative and invasive properties [ 13] . LncRNAs have microRNA Responsible Elements (MRE),a sponge binding site for miRNAs, in order to regulate speci c miRNA-orchestrated target transcript downregulation [ 14] .Chen and colleagues highlighted lncRNA CRNDE to promote angiogenesis within hepatoblastoma through targeted activity on the miR-203 / VEGFA axis [ 15] . Zhu et al con rmed that CRNDE promotes proliferative / angiogenesis properties by pancreatic cancer through regulation of miR-451a and CDKN2D [ 16] .…”