EIF4A3-induced circ_0084615 contributes to the progression of colorectal cancer via miR-599/ONECUT2 pathway

Jiang, Zhipeng; Tai, Qin-wen; Xie, Xiaojun; Hou, Zehui; Liu, Wei; Yu, Zhenning; Liang, Zhiqiang; Chen, Shuang

doi:10.1186/s13046-021-02029-y

Cited by 41 publications

(29 citation statements)

References 29 publications

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“…7A ). Previous studies have proved that EIF4A3, a core component of the exon junction complex, play an essential role in pre-mRNA splicing and could induce circular RNA formation via binding to the upstream region of some particular mRNAs 20 . Therefore, we conduced RIP assay using anti-EIF4A3 antibody and confirmed the enrichment of PRKCI mRNA in EIF4A3 precipitates compared with the negative control (Fig.…”

Section: Resultsmentioning

confidence: 99%

EIF4A3-mediated circPRKCI expression promotes triple-negative breast cancer progression by regulating WBP2 and PI3K/AKT signaling pathway

et al. 2022

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Triple-negative breast cancer (TNBC) is known as a highly aggressive subtype of BC due to high rate of recurrence and metastasis, poor prognosis and lacking of effective targeted therapies. Circular RNAs (circRNAs) have been reported to participate in the progression of TNBC. In this study, we demonstrated that circPRKCI, derived from the PRKCI gene, was elevated in BC tissues and cell lines, especially in TNBC. The functional investigation showed that circPRKCI could significantly promote the proliferation and migration of TNBC in vivo and in vitro. In addition, circPRKCI regulated WBP2 and the phosphorylation of AKT via serving as miR-545-3p sponge. Of note, EIF4A3 could induce circPRKCI expression and nuclear export in TNBC cells. Taken together, EIF4A3-mediated circPRKCI could promote TNBC progression by regulating WBP2 and PI3K/AKT signaling pathway, providing a new avenue of therapy for TNBC.

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Section: Resultsmentioning

confidence: 99%

EIF4A3-mediated circPRKCI expression promotes triple-negative breast cancer progression by regulating WBP2 and PI3K/AKT signaling pathway

et al. 2022

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“…Aberrant expression of circRNAs plays a crucial role in the development of many cancers (25)(26)(27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

EIF4A3-induced Circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p/RNF113A pathway

Yang

Han

et al. 2022

Preprint

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Aberrant expression of circRNAs has been proven to play a crucial role in the progression of acute myeloid leukemia (AML), but its regulatory mechanism remains unclear. Herein, we identify a novel m6A modification-related circRNA, Circ_0001187, which is downregulated in AML patients, and its low level contributes to a poor prognosis. We find that the expression of Circ_0001187 is regulated by the modification of DNA methylation and histone acetylation, and its biogenesis is meditated by splicing factor EIF4A3. Knockdown of Circ_0001187 significantly promotes the proliferation and inhibits the apoptosis of AML cells in vitro and in vivo, while overexpression of Circ_0001187 exerts the opposite effects. Moreover, we prove that Circ_0001187 enhances METTL3 protein degradation, which further decreases mRNA m6A modification in AML cells. Mechanistically, Circ_0001187 sponges miR-499a-5p to enhance the expression RNF113A. And RNF113A functions as an E3 ubiquitin ligase to mediate METTL3 ubiquitin/proteasome-dependent degradation by K48-linked polyubiquitin chains. Collectively, our findings highlight the potential clinical implications of Circ_0001187 as a key tumor suppressor of AML via the miR-499a-5p/RNF113A/METTL3 pathway.

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“…Recent studies described novel ONECUT2 regulatory mechanisms. In CRC, circular RNA (circ_0084615) serves as a sponge for miR-599, which directly binds to ONECUT2 [ 54 ]. Furthermore, studies on CRC cells showed that by silencing circ_0084615, EMT-related markers ZEB2 and vimentin are reduced and E-cadherin is elevated.…”

Section: Discussionmentioning

confidence: 99%

miR-200b, ZEB2 and PTPN13 Are Downregulated in Colorectal Carcinoma with Serosal Invasion

et al. 2022

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Serosal invasion is an independent negative prognostic factor in certain cancers, including CRC. However, the mechanisms behind serosal invasion are poorly understood. We therefore assumed that epithelial-mesenchymal transition (EMT) might be involved. Our study included 34 patients with CRC, 3 stage pT2, 14 stage pT3 and 17 showing serosal invasion (stage pT4a according to TNM staging system). RNA isolated from formalin-fixed paraffin-embedded tissue samples was analysed for expression of the miR-200 family and their target genes CDKN1B, ONECUT2, PTPN13, RND3, SOX2, TGFB2 and ZEB2 using real-time PCR. We found upregulation of miR-200b and ONECUT2 in CRC pT3 and pT4a compared to normal mucosa, and downregulation of CDKN1B in CRC pT3. Moreover, we observed, downregulation of miR-200b, PTPN13 and ZEB2 in CRC with serosal invasion (pT4a) compared to pT3. Our results suggest the involvement of partial EMT in serosal invasion of CRC. In addition, PTPN13 seems to be one of the important regulators involved in serosal invasion, and ONECUT2 in tumour growth.

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EIF4A3-induced circ_0084615 contributes to the progression of colorectal cancer via miR-599/ONECUT2 pathway

Cited by 41 publications

References 29 publications

EIF4A3-mediated circPRKCI expression promotes triple-negative breast cancer progression by regulating WBP2 and PI3K/AKT signaling pathway

EIF4A3-mediated circPRKCI expression promotes triple-negative breast cancer progression by regulating WBP2 and PI3K/AKT signaling pathway

EIF4A3-induced Circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p/RNF113A pathway

miR-200b, ZEB2 and PTPN13 Are Downregulated in Colorectal Carcinoma with Serosal Invasion

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