CELF2 suppresses non-small cell lung carcinoma growth by inhibiting the PREX2-PTEN interaction

Yeung, Yiu To; Fan, Suyu; Lu, Bingbing; Yin, Shuying; Yang, Sen; Nie, Wenna; Wang, Meixian; Zhou, Liting; Li, Tiepeng; Li, Xiang; Bode, Ann M.; Dong, Zigang

doi:10.1093/carcin/bgz113

Cited by 45 publications

(41 citation statements)

References 41 publications

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“…In nonsmall cell lung cancer, CELF2 could inhibit the phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2 (PREX2)-phosphatase and tensin homolog (PTEN) interaction. Overexpression of CELF2 could significantly inhibit tumor growth in vivo or in vitro through inhibiting the PI3K/AKT signaling pathway phosphorylation 26 .…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: LncRNA CCDC26 Interacts with CELF2 Protein to Enhance Myeloid Leukemia Cell Proliferation and Invasion via the circRNA_ANKIB1/miR-195-5p/PRR11 Axis

Shi

et al. 2021

Cell Transplant

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LncRNA CCDC26 is aberrantly expressed in myeloid leukemia (ML) and promotes myeloid leukemia progression, but the potential mechanism of CCDC26 in regulating ML progression is unclear. In this study, we observed that lncRNA CCDC26 was upregulated in both chronic and acute ML cell lines. LncRNA CCDC26 promoted the proliferation and invasion of K562 and HL-60 cells, which was determined by cell counting kit-8 test and Transwell invasion assay. Flow cytometry showed that lncRNA CCDC26 inhibited cell apoptosis. Bioinformatics and expression correlation analyses revealed that there was a potential interaction between CCDC26 and CUGBP Elav-like family member 2 (CELF2) protein, an RNA bind protein (RBP). Then the relationship between CCDC26 and the RBP CELF2 was identified by using RNA pull-down and RNA immunoprecipitation (RNA-IP) assays. Further analysis showed that overexpression of CCDC26 could noticeably upregulate circRNA_ANKIB1 expression via sponging CELF2. Subsequently, we found that overexpressed circRNA_ANKIB1 could significantly promote proline rich 11 (PRR11) protein expression by sponging miR-195a-5p. Moreover, PRR11 was also upregulated by CCDC26 and downregulated by CELF2. Mechanically, we uncovered that the miR-195a-5p inhibitor activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways through upregulating PRR11 protein expression. Furthermore, the inhibitors of AKT, p65-NF-κB, or Bcl-2 could inhibit the effect of the miR-195a-5p inhibitor on ML cell behaviors. In conclusion, lncRNA CCDC26 could upregulate PRR11 protein expression by sponging miR-195a-5p, thereby activating the PI3K/AKT and NF-κB pathways to enhance ML cell proliferation and invasion and suppress cell apoptosis.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: LncRNA CCDC26 Interacts with CELF2 Protein to Enhance Myeloid Leukemia Cell Proliferation and Invasion via the circRNA_ANKIB1/miR-195-5p/PRR11 Axis

Shi

et al. 2021

Cell Transplant

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“…CELF2 is an RNA-binding protein of the CELF family that acts as a tumor suppressor and is positively correlated with the prognosis of various tumors, such as non-small cell lung carcinoma ( 25 ), gastric cancer ( 26 ), and pancreatic cancer ( 27 ). The main biological functions of CELF2 are promoting apoptosis as well as inhibiting proliferation and migration We found in this analysis that patients with high expression of CELF2 had a better prognosis, in line with those previous studies.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Prognostic Alternative Splicing Signatures in Oral Squamous Cell Carcinoma

et al. 2020

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Background Alternative splicing (AS) plays an essential role in tumorigenesis and progression. This study aimed to develop a novel prognostic model based on the AS events to obtain more accurate survival prediction and search for potential therapeutic targets in oral squamous cell carcinoma (OSCC). Methods Seven types of AS events in 326 OSCC patients with RNA-seq were obtained from the TCGA SpliceSeq tool and the TCGA database. Cox analysis, the least absolute shrinkage and selection operator Cox regression and random forest were employed to establish prognostic models. Genomics of Drug Sensitivity in Cancer (GDSC) was adopted to estimate the possible drug sensiticity. Prognostic splicing factor (SF)-AS network was constructed by Cytoscape. Results The final model included 12 AS events, showing satisfactory performance. The area under the curve for 3- and 5-year survival in the training cohort was 0.83 and 0.82, respectively while that in internal validation was 0.83 and 0.82 accordingly. The calibration curve also indicated a satisfactory agreement between the observation and the predictive values. Low-risk patients stratified by the final model presented higher sensitivity to three chemo drugs. Besides, the prognostic SF-AS regulatory network contained five key SFs and 62 AS events. Conclusions We developed a powerful prognostic AS signature for OSCC and deepened the understanding of SF-AS network regulatory mechanisms. Low-risk patients tended to be more sensitive to the three chemo drugs while five key SFs including CELF2, TIA1, HNRNPC, HNRNPK, and SRSF9 were identified as potential prognostic biomarkers, which may offer new prospects for effective therapies of OSCC.

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“…The CELF2 gene is located on chromosome 10p, a region frequently lost in human cancers, 23 , 24 suggesting that the region encoding CELF2 potentially encodes tumor suppressors. The role of CELF2 as a tumor suppressor has been studied in multiple types of cancer, including colon cancer, 25 pancreatic cancer, 20 lung cancer, 26 gastric cancer, 27 and breast cancer. 28 However, the functional role of CELF2 in ovarian cancer has not yet been identified.…”

Section: Discussionmentioning

confidence: 99%

The RNA-Binding Protein CELF2 Inhibits Ovarian Cancer Progression by Stabilizing FAM198B

Guo

et al. 2021

Molecular Therapy - Nucleic Acids

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An increasing number of studies have clarified the functional roles of RNA-binding proteins (RBPs) in driving post-transcriptional mechanisms of cancer progression. In this study, we integrated data from the RBP database and Gene Expression Omnibus (GEO) data with RNA sequencing (RNA-seq) data from 10 ovarian cancer tissues and 8 normal ovarian tissues and identified an RBP, CUGBP- and ETR-3-like family 2 (CELF2). We found that CELF2 expression was downregulated in ovarian cancer and positively correlated with the overall survival (OS) and progression-free survival (PFS) of patients with ovarian cancer. Altered CELF2 expression led to changes in the proliferation, migration, and invasion of ovarian cancer cells in vitro and in vivo . CELF2 expression increased the stability of its target, FAM198B, by binding to AU/U-rich elements (AREs) in the 3′ untranslated region (3′ UTR). FAM198B knockdown restored the CELF2-mediated suppression of proliferation and migration. We also found that CELF2/FAM198B may repress ovarian cancer progression by inhibiting the mitogen-activated protein kinase/extracellular-regulated protein kinase (MAPK/ERK) signaling pathway. Finally, a curcumin-induced increase in CELF2 expression resulted in increased ovarian cancer cell sensitivity to cisplatin. Our study elucidated a novel mechanism by which the CELF2/FAM198B axis regulates proliferation and metastasis in ovarian cancer, providing novel, potential therapeutic targets for ovarian cancer.

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CELF2 suppresses non-small cell lung carcinoma growth by inhibiting the PREX2-PTEN interaction

Cited by 45 publications

References 41 publications

RETRACTED: LncRNA CCDC26 Interacts with CELF2 Protein to Enhance Myeloid Leukemia Cell Proliferation and Invasion via the circRNA_ANKIB1/miR-195-5p/PRR11 Axis

RETRACTED: LncRNA CCDC26 Interacts with CELF2 Protein to Enhance Myeloid Leukemia Cell Proliferation and Invasion via the circRNA_ANKIB1/miR-195-5p/PRR11 Axis

Comprehensive Analysis of Prognostic Alternative Splicing Signatures in Oral Squamous Cell Carcinoma

The RNA-Binding Protein CELF2 Inhibits Ovarian Cancer Progression by Stabilizing FAM198B

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