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Long Non-Coding RNA CRYBG3 Promotes Lung Cancer Metastasis via Activating the eEF1A1/MDM2/MTBP Axis
Anqing Wu1,2, Jiaxin Tang1,2, Ziyang Guo1,2
1State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.
Abstract:
The occurrence of distant tumor metastases is a major barrier in non-small cell lung cancer (NSCLC) therapy, and seriously affects clinical treatment and patient prognosis. Recently, long non-coding RNAs (lncRNAs) have been demonstrated to be crucial regulators of metastasis in lung cancer. The aim of this study was to reveal the underlying mechanisms of a novel lncRNA LNC CRYBG3 in regulating NSCLC metastasis. Experimental results showed that LNC CRYBG3 was upregulated in NSCLC cells compared with normal tissue cells, and its level was involved in these cells' metastatic ability. Exogenously overexpressed LNC CRYBG3 increased the metastatic ability and the protein expression level of the metastasis-associated proteins Snail and Vimentin in low metastatic lung cancer HCC827 cell line. In addition, LNC CRYBG3 contributed to HCC827 cell metastasis in vivo. Mechanistically, LNC CRYBG3 could directly combine with eEF1A1 and promote it to move into the nucleus to enhance the transcription of MDM2. Overexpressed MDM2 combined with MDM2 binding protein (MTBP) to reduce the binding of MTBP with ACTN4 and consequently increased cell migration mediated by ACTN4. In conclusion, the LNC CRYBG3/eEF1A1/MDM2/MTBP axis is a novel signaling pathway regulating tumor metastasis and may be a potential therapeutic target for NSCLC treatment.
Insights
A novel long non-coding RNA (lncRNA), LNC CRYBG3, promotes non-small cell lung cancer (NSCLC) metastasis by regulating the eEF1A1/MDM2/MTBP/ACTN4 pathway. This discovery offers a potential new therapeutic target for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Distant tumor metastases significantly impede non-small cell lung cancer (NSCLC) treatment and patient outcomes.
- Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of metastasis in lung cancer.
Purpose of the Study:
- To investigate the role and underlying mechanisms of the novel long non-coding RNA (lncRNA) LNC CRYBG3 in regulating NSCLC metastasis.
Main Methods:
- Quantitative analysis of LNC CRYBG3 expression in NSCLC cells versus normal tissues.
- In vitro experiments involving overexpression of LNC CRYBG3 in HCC827 cells to assess metastatic potential and protein expression.
- In vivo metastasis assays.
- Mechanistic studies to elucidate the interaction of LNC CRYBG3 with eEF1A1, MDM2, MTBP, and ACTN4.
Main Results:
- LNC CRYBG3 was found to be upregulated in NSCLC cells and correlated with metastatic ability.
- Overexpression of LNC CRYBG3 enhanced metastasis and increased Snail and Vimentin protein levels in HCC827 cells, both in vitro and in vivo.
- LNC CRYBG3 directly binds to eEF1A1, promoting nuclear translocation and enhancing MDM2 transcription. This leads to MDM2/MTBP complex formation, disrupting MTBP/ACTN4 binding and increasing cell migration.
Conclusions:
- The LNC CRYBG3/eEF1A1/MDM2/MTBP axis represents a newly identified signaling pathway crucial for regulating tumor metastasis in NSCLC.
- LNC CRYBG3 emerges as a potential therapeutic target for managing NSCLC metastasis.
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