| Yan Deng,Zhengguang He,Xiaobin Luo,Rong Qiu,Yong Zhao,Wen Luo. MiR-183-5p promotes the progression of non-small cell lung cancer through targeted regulation of FOXO1. Oncol Transl Med, 2023, 9: 121-132. |
| MiR-183-5p promotes the progression of non-small cell lung cancer through targeted regulation of FOXO1 |
| Received:October 12, 2022 Revised:May 23, 2023 |
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| KeyWord:non-small cell lung cancer; miR-183-5p; forkhead box protein O1; malignant biological behavior; targeted regulation |
| Author Name | Affiliation | E-mail | | Yan Deng | Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining 629000, China | zipydw@163.com | | Zhengguang He | Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining 629000, China | | | Xiaobin Luo | Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining 629000, China | | | Rong Qiu | Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining 629000, China | | | Yong Zhao | Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining 629000, China | | | Wen Luo | Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining 629000, China | |
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| Abstract: |
| Objective To investigate miR-183-5p targeting to forkhead box protein O1 (FOXO1) and its corresponding
effect on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of non-small
cell lung cancer (NSCLC) cells.
Methods NSCLC tissues and adjacent normal tissues from 60 patients with NSCLC adenocarcinoma
were obtained via pathological biopsy or intraoperative resection. Several cell lines were cultured in
vitro, including the human normal lung epithelial cell line BEAS-2B and human NSCLC cell lines A549,
SPCA-1, PC-9, and 95-D. miR-183-5p and FOXO1 mRNA expression in tissues and cells were detected
by qRT-PCR; the corresponding correlations in NSCLC tissues were analyzed using the Pearson test,
and the relationship between miR-183-5p expression and clinicopathological parameters was analyzed.
The miR-183-5p-mediated regulation of FOXO1 was verified by bioinformatics prediction alongside double
luciferase, RNA-binding protein immunoprecipitation (RIP) assay, and pull-down experiments. A549 cells
were divided into control, anti-miR-NC, anti-miR-183-5p, miR-NC, miR-183-5p, miR-183-5p+pcDNA3.1,
and miR-183-5p+pcDNA3.1-FOXO1 groups. Cell proliferation, invasion, migration, apoptosis, and cell
cycle distribution were detected using an MTT assay, clone formation assay, Transwell assay, scratch
test, and flow cytometry, respectively. The expression of EMT-related proteins in the cells was analyzed
by western blotting. The effect of miR-185-3p silencing on the development of transplanted tumors was
detected by analyzing tumor formation in nude mice.
Results miR-183-5p expression was significantly higher in NSCLC tissues and cells than in adjacent
normal tissues, whereas FOXO1 mRNA expression was significantly down-regulated. There was a
significant negative correlation between miR-183-5p and FOXO1 mRNA in NSCLC tissues (P < 0.05).
Additionally, the expression of miR-183-5p was significantly correlated with tumor size, tumor differentiation,
and tumor-node-metastasis stage in patients with NSCLC (P < 0.05). miR-183-5p targeted and inhibited
FOXO1 expression. Compared to the anti-miR-NC group, the cell proliferation, scratch healing rate,
N-cadherin and vimentin protein expression, and the proportion of S phase cells were significantly lower in
the anti-miR-183-5p group, whereas the protein expression of E-cadherin and α-catenin and the proportion
of G0/G1 phase cells were significantly higher; additionally, the frequency of colony formation and invasion
were significantly lower in the anti-miR-183-5p group (P < 0.05). Compared to the miR-NC group, the
cell proliferation, scratch healing rate, N-cadherin and vimentin protein expression, and the proportion of
S phase cells in the miR-183-5p group were significantly higher, whereas the E-cadherin and α-catenin
protein expression and the proportion of G0/G1 phase cells were significantly lower; furthermore, the
frequency of colony formation and invasion were significantly higher in the miR-183-5p group (P < 0.05).
Compared with the miR-183-5p+pcDNA3.1 group, the OD value, scratch healing rate, N-cadherin and
vimentin protein expression, and the proportion of S phase cells were significantly lower in the miR-183-
5p+pcDNA3.1-FOXO1 group, whereas E-cadherin and α-catenin protein expression and the proportion of
G0/G1 phase cells were significantly higher; additionally, the frequency of colony formation and invasion
was significantly lower in the miR-183-5p+pcDNA3.1-FOXO1 group (P < 0.05). Overall, silencing miR-185-
3p inhibited the growth of transplanted tumors and promoted FOXO1 expression.
Conclusion Overexpression of miR-183-5p can inhibit apoptosis and promote the proliferation, migration,
invasion, and EMT, of NSCLC cells by down-regulating FOXO1 expression. |
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