RETRACTED: LINC00472 Acts as a Tumor Suppressor in NSCLC through KLLN-Mediated p53-Signaling Pathway via MicroRNA-149-3p and MicroRNA-4270

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.

Long non‑coding RNA maternally expressed gene regulates cigarette smoke extract induced lung inflammation and human bronchial epithelial apoptosis via miR‑149‑3p

“…In addition, in the present study, MEG3 regulated the NF-κB signaling pathway in HBE cells by targeting miR-149-3p. It has been reported that miR-149-3p is involved in the Akt1 signaling pathway in pancreatic cancer ( 40 ) and in the p53-signaling pathway in non-small-cell lung cancer ( 41 ). Future studies should focus on whether the regulatory effects of MEG3/miR-149-3p in COPD may be mediated by other signaling pathways.…”

MicroRNA‑149‑3p inhibits cell proliferation by targeting AKT2 in oral squamous cell carcinoma

“…However, miR-149-5p and miR-149-3p exhibit diverse roles in cancer progression. For example, long intergenic non-protein-coding RNA 472 inhibited tumor growth and metastasis by sponging and decreasing miR-149-3p expression, leading to the upregulation of KLLN and activation of p53 signaling in non-small cell lung cancer (NSCLC) cells, which suggested an oncogenic function of miR-149-3p ( 25 ). Conversely, miR-149-5p acted as a tumor suppressor in NSCLC ( 26 , 27 ).…”

Long non‐coding RNAs as potential biomarkers in the prognosis and diagnosis of lung cancer: A review and target analysis

“…Zou et al identified that LINC00472 upregulation prevents the cell invasion, metastasis, and growth in NCI‐H1299 Cells. They also demonstrated that the upregulation of LINC00472 activates the p53‐signaling pathway, decreases cell invasion and metastasis in H1299 cell line via sponging miR‐4270 and miR‐149‐3p 77 …”

“…They also demonstrated that the upregulation of LINC00472 activates the p53-signaling pathway, decreases cell invasion and metastasis in H1299 cell line via sponging miR-4270 and miR-149-3p . 77…”