Long Non-Coding RNA CRYBG3 Promotes Lung Cancer Metastasis via Activating the eEF1A1/MDM2/MTBP Axis

Wu, Anqing; Tang, Jiaxin; Guo, Ziyang; Dai, Yingchu; Nie, Jing; Hu, Wentao; Liu, Ning-Ang; Ye, Caiyong; Li, Shihong; Pei, Hailong; Zhou, Guangming

doi:10.3390/ijms22063211

Cited by 13 publications

(9 citation statements)

References 32 publications

(42 reference statements)

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“…It had been confirmed in previous studies that EEF1A1 made oncogenic functions in various tumors, such as lung cancer [ 20 ], renal cell carcinoma [ 21 ], hepatocellular carcinoma [ 22 ], and GC [ 23 , 24 ], etc. Besides, EEF1A1 expression level is associated with poor prognosis in GC based on the Cancer Genome Atlas (TCGA) database (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 78%

A novel 3’tRNA-derived fragment tRF-Val promotes proliferation and inhibits apoptosis by targeting EEF1A1 in gastric cancer

Cui

et al. 2022

Cell Death Dis

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At present, it is commonly believed that tRFs and tiRNAs are formed by the specific and selective shear of tRNAs under certain pressure stimulation, rather than by random degradation of tRNA. tRFs and tiRNAs have been reported to contribute to the biological process of a variety of human cancers. However, the evidence for the mechanisms of tRFs and tiRNAs in the occurrence and development of gastric cancer (GC) is still insufficient. Here, we aimed to explore the carcinogenic roles of tRFs and tiRNAs in GC with RNA-sequencing technique, and found a novel 3’tRNA-derived fragment tRF-Val was significantly upregulated in GC tissues and cell lines. tRF-Val expression was positively correlated with tumor size and the depth of tumor invasion in GC tissues. Functionally, tRF-Val promoted proliferation and invasion, and inhibited apoptosis in GC cells. Mechanistically, tRF-Val directly bound to the chaperone molecule EEF1A1, mediated its transport into the nucleus and promoted its interaction with MDM2 (a specific p53 E3 ubiquitin ligase), thus inhibiting the downstream molecular pathway of p53 and promoting GC progression. These findings provided a new potential therapeutic target for GC and a new explanation for the occurrence of GC.

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Section: Resultsmentioning

confidence: 78%

A novel 3’tRNA-derived fragment tRF-Val promotes proliferation and inhibits apoptosis by targeting EEF1A1 in gastric cancer

Cui

et al. 2022

Cell Death Dis

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“… 13 , 34 For instance, Wu A. et al found that eEF1A1 could directly target the promoter region of murine double minute 2 to regulate the expression and promote lung cancer metastasis. 36 In this study, the WGCNA algorithm was used to discover the core genes. The method of using the WGCNA algorithm to discover the core genes by screening clinical feature‐related gene co‐expression networks is well‐established.…”

Section: Discussionmentioning

confidence: 99%

eEF1A1 promotes colorectal cancer progression and predicts poor prognosis of patients

et al. 2022

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Colorectal cancer (CRC) is a major leading cause of cancer mortality worldwide in which dysregulated protein synthesis plays an etiologic role. The eukaryotic elongation factor 1 A1 (eEF1A1) exerts significant effects on protein synthesis by contributing to peptide chain extension. Whereas its role in CRC remains to be investigated. In this study, we found that the mRNA and protein levels of eEF1A1 were significantly upregulated in CRC cell lines and tissues. Elevated expression of eEF1A1 was correlated with shorter overall survival in 94 CRC patients. The inhibition of proliferation and cell cycle block were observed in CRC cells after eEF1A1 downregulation. Mechanistically, weighted gene correlation network analysis and further Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that mitogen‐activated protein kinases (MAPKs) signaling pathways were significantly enriched in high‐eEF1A1 expression group, and the levels of phosphorylated p38/JNK/ERK MAPK were dramatically decreased after eEF1A1 downregulation. Overexpression of eEF1A1 in CRC correlated with a poor prognosis. Collectively, this study determined the oncogenic role of eEF1A1 in CRC proliferation and tumorigenesis. eEF1A1 might be a promising therapeutic target and prognostic biomarker in CRC.

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“…The Ion 318 ™ Chip v2 BC chip used in this study can sequence 96 samples at a time. It can not only provide new research methods for methylation-related research, but also provides new ideas for the epigenetic-related research (67)(68)(69)(70).…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

et al. 2021

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The pro-oncogene ETS-1 (E26 transformation-specific sequence 1) is a key regulator of the proliferation and invasion of cancer cells. The present work examined the correlation of the aberrant expression of ETS-1 with histological or clinical classification of astrocytoma: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). MicroRNA, miR-338-5p, was predicted by an online tool (miRDB) to potentially target the 3’ untranslated region of ETS-1; this was confirmed by multi-assays, including western blot experiments or the point mutation of the targeting sites of miR-338-5p in ETS-1’s 3’untralation region (3’UTR). The expression of miR-338-5p was negatively associated with that of ETS-1 in astrocytoma, and deficiency of miR-338-5p would mediate aberrant expression of ETS-1 in astrocytoma. Mechanistically, hypermethylation of miR-338-5p by DNA methyltransferase 1 (DNMT1) resulted in repression of miR-338-5p expression and the aberrant expression of ETS-1. Knockdown or deactivation of DNMT1 decreased the methylation rate of the miR-338-5p promoter, increased the expression of miR-338-5p, and repressed the expression of ETS-1 in astrocytoma cell lines U251 and U87. These results indicate that hypermethylation of the miR-338-5p promoter by DNMT1 mediates the aberrant expression of ETS-1 related to disease severity of patients with astrocytoma.

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Long Non-Coding RNA CRYBG3 Promotes Lung Cancer Metastasis via Activating the eEF1A1/MDM2/MTBP Axis

Cited by 13 publications

References 32 publications

A novel 3’tRNA-derived fragment tRF-Val promotes proliferation and inhibits apoptosis by targeting EEF1A1 in gastric cancer

A novel 3’tRNA-derived fragment tRF-Val promotes proliferation and inhibits apoptosis by targeting EEF1A1 in gastric cancer

eEF1A1 promotes colorectal cancer progression and predicts poor prognosis of patients

Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

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