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Published on: August 23, 2019
LINC00472 Acts as a Tumor Suppressor in NSCLC through KLLN-Mediated p53-Signaling Pathway via MicroRNA-149-3p and
Aimei Zou1, Xingli Liu1, Zongjiong Mai2
1Department of Oncology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan 528308, P.R. China.
Abstract:
Long non-coding RNAs and microRNAs (miRNAs) have been reported to participate in the progression of non-small-cell lung cancer (NSCLC). Long intergenic non-protein-coding RNA 472 (LINC00472), miR-149-3p, and miR-4270 were found to be involved in tumor activities, suggesting potential roles in NSCLC. Thus, this study aimed to examine the ability of LINC00472 to influence the progression of NSCLC with the involvement of miR-149-3p and miR-4270. Initially, differentially expressed long non-coding RNAs (lncRNAs), downstream regulatory miRNAs, and genes related to NSCLC were identified. Next, the interaction among LINC00472, miR-149-3p and miR-4270, and KLLN and the p53-signaling pathway was determined. The effect of LINC00472 on the expression of E-cadherin, N-cadherin, and Vimentin was examined through gain-of-function and loss-of-function experiments. Lastly, the effects of LINC00472 on NSCLC tumor growth were assessed in vivo. LINC00472 and KLLN were found to exhibit low levels, while miR-149-3p and miR-4270 were highly expressed in NSCLC. In addition, the overexpression of LINC00472 was observed to upregulate KLLN and activate the p53-signaling pathway, which ultimately inhibited the invasion, migration, and EMT of NSCLC cells via miR-149-3p and miR-4270, corresponding to decreased N-cadherin and Vimentin and increased E-cadherin. The overexpression of LINC00472 exerted an inhibitory effect on tumor growth in vivo. Taken together, the key evidence suggests that the overexpression of LINC00472 can downregulate miR-149-3p and miR-4270 to upregulate KLLN and activate the p53-signaling pathway, thus inhibiting the development of NSCLC. This study highlights the potential of LINC00472 as a promising therapeutic target for NSCLC treatment.
Insights
Long intergenic non-protein-coding RNA 472 (LINC00472) inhibits non-small-cell lung cancer (NSCLC) progression by downregulating oncogenic miRNAs and activating tumor-suppressive pathways. This study reveals LINC00472 as a potential therapeutic target for NSCLC.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are implicated in non-small-cell lung cancer (NSCLC) pathogenesis.
- Specific roles of LINC00472, miR-149-3p, and miR-4270 in NSCLC progression require elucidation.
Purpose of the Study:
- To investigate the influence of LINC00472 on NSCLC progression, focusing on its interaction with miR-149-3p and miR-4270.
- To explore the molecular mechanisms underlying LINC00472's effects on NSCLC cell invasion, migration, and epithelial-mesenchymal transition (EMT).
Main Methods:
- Differential expression analysis of lncRNAs, miRNAs, and genes in NSCLC.
- Investigation of the regulatory network involving LINC00472, miR-149-3p, miR-4270, KLLN, and the p53-signaling pathway.
- Gain- and loss-of-function experiments to assess LINC00472's impact on EMT markers (E-cadherin, N-cadherin, Vimentin).
- In vivo studies to evaluate LINC00472's effect on NSCLC tumor growth.
Main Results:
- LINC00472 and KLLN were downregulated, while miR-149-3p and miR-4270 were upregulated in NSCLC.
- Overexpression of LINC00472 upregulated KLLN, activated the p53-signaling pathway, and inhibited NSCLC cell invasion, migration, and EMT.
- LINC00472 overexpression decreased N-cadherin and Vimentin while increasing E-cadherin expression.
- In vivo, LINC00472 overexpression significantly inhibited NSCLC tumor growth.
Conclusions:
- LINC00472 functions as a tumor suppressor in NSCLC by downregulating miR-149-3p and miR-4270, subsequently upregulating KLLN and activating the p53 pathway.
- These molecular events collectively inhibit NSCLC development, invasion, migration, and EMT.
- LINC00472 represents a promising therapeutic target for NSCLC treatment.
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