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. 2022 Aug 14:2022:3110330.
doi: 10.1155/2022/3110330. eCollection 2022.

miR-29b Regulates Lung Cancer Progression by Downregulating FEM1B and Inhibiting the FOX01/AKT Pathway

Huanrong Zhang  1 , Rong Wang  1 , Qiuhua Deng  2
Affiliations

miR-29b Regulates Lung Cancer Progression by Downregulating FEM1B and Inhibiting the FOX01/AKT Pathway

Huanrong Zhang et al. Comput Math Methods Med. .

Retraction in

Abstract

Purpose: Lung cancer is a relatively common type of cancer, and the incidence rate has been on the rise in recent years. MicroRNAs are a class of endogenous small RNA molecules, which are essential for the posttranscriptional regulation of genes. miR-29b is closely related to the occurrence and development of tumors, including prostate cancer, colon cancer, and breast cancer. However, few studies have been performed to explore the expression and pathway of miR-29b in non-small-cell lung cancer (NSCLC).

Methods: Using bioinformatics analysis, we found that patients with low relative expression of the miR-29b gene have a low long-term survival rate. The results of in vitro research showed that when miR-29b expression was upregulated, the invasion, migration, and proliferation of A549 and NCI-H-1792 cells was inhibited, and the apoptosis was accelerated.

Results: The results showed that FEM1B is a miR-29b target gene, and the expressions of FEM1B and miR-29b were negatively correlated. Like the upregulation of miR-29b expression, silencing the FEM1B expression could also impair the invasion, migration, and proliferation abilities of A549 and NCI-H-1792 cells. When FEM1B expression was restored, the inhibitory effect of miR-29b could be reversed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB) analysis showed that overexpression of miR-29b could inhibit the expression of FEM1B, AKT, vascular endothelial growth factor (VEGF), and Sirt3 in A549 and NCI-H-1792 cells and upregulate the expression of FOXO1 protein.

Conclusion: The results of this study indicate that miR-29b inhibits the proliferation and deterioration of NSCLC cells by targeting FEM1B and inhibiting the activation of the FOXO1/AKT pathway. miR-29b may become a new target for the clinical diagnosis and treatment of lung cancer, and it is expected to become a new inhibitor of NSCLC.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
The expression of miR-29b is significantly reduced in non-small-cell lung cancer (NSCLC) cell proliferation, invasion, and metastasis of NSCLC cells in vitro. (a) GDS4794 from the GEO data set was collected, and paracancerous and lung cancer tumor samples were analyzed. (b) miR-29b expression was decreased in NSCLC cells. (c) The survival rate of lung cancer patients was analyzed using the data downloaded from The Cancer Genome Atlas (TCGA) database.
Figure 2
Figure 2
Overexpression of miR-29b inhibits the growth of NSCLC cells. (a) miR-29b expression was increased significantly after overexpression of miR-29b. (b) miR-29b inhibited the proliferation of A549 and NCI-H1792 cells. (c) miR-29b inhibited the formation of A549 and NCI-H-1792 cell clones. (d) miR-29b inhibited A549 and NCI-H-1792 cell invasion. (e) miR-29b inhibited A549 and NCI-H-1792 cell migration. (f) miR-29b promoted the apoptosis of A549 and NCI-H1792 cells. (g) miR-29b promotes apoptosis of A549 and nci-h1792 cells in G0-G1 phase. ∗P ≤ 0.05, comparison between the miR-29b group and miR-NC group.
Figure 3
Figure 3
FEM1B is a miR-29b regulatory target gene. (a) The predicted miR-29b binding site in the 3′-UTR of FEM1B and the mutated 3′-UTR of FEM1B, which were generated using the complementary sequence in the seed region of miR-29b. (b) miR-29b or NC and a luciferase vector encoding the WT or MUT FEM1B 3′-UTR were transfected into 293T cells, and the relative luciferase activity was measured. (c) Overexpression of miR-29b inhibited the expression of FEM1B mRNA in NSCLC cells. (d) Overexpression of miR-29b inhibited the expression of FEM1B protein in NSCLC cells; ∗P ≤ 0.05 compared with the NC-A549 group; #P ≤ 0.05 compared with the NC-NCI-H-1792 group.
Figure 4
Figure 4
Downregulation of FEM1B inhibits the proliferation, invasion, and metastasis of lung cancer cells. (a and b) FEM1B mRNA expression in NSCLC cells was significantly reduced after inhibiting FEM1B. (c) FEM1B was downregulated or miR-29b was overexpressed to inhibit the proliferation of A549 and NCI-H-1792 cells. (d and e) FEM1B was downregulated or miR-29b was overexpressed, and A549 cells inhibited the migration of NCI-H-1792 cells. (f) Downregulation of FEM1B or overexpression of miR-29b inhibited the invasion of A549 and NCI-H-1792 cells. ∗P ≤ 0.05, comparison between the miR-29b group and NC-group. #P ≤ 0.05, comparison between the si-FEM1B group and NC group.
Figure 5
Figure 5
miR-29b inhibits the growth of NSCLC tissues in mice. (a) The change trend in mouse body weight. (b) miR-29b inhibited the growth of NSCLC tissue. (c) miR-29b inhibited the expression of FEM1B in mouse NSCLC tissue. (d) miR-29b inhibits TNF in tumor tissues of NSCLC mice and VEGF to promote the expression of IL-10. ∗P ≤ 0.05, comparison between the miR-29b group and NC-A549 group; #P ≤ 0.05, comparison between the NC-A549 group and control group.
Figure 6
Figure 6
The effect of miR-29b expression on the downstream molecules in the signaling pathway. (a) RT-PCR showed that the expression level of HIF-1α, Sirt1, and AKT was decreased when miR-29b was overexpressed, while the level of TNF-α and FOX01 was increased when miR-29b was overexpressed. The siFEMB1 reversed this phenomenon. (b) The results of WB showed that when miR-29b was overexpressed, the expression levels of SMAD3 and Sirt3 were decreased and the TNF-α, VEGF, and FOX01 were increased. And the overexpression of FEM1B augments this phenomenon. (c) The expression ability of downstream molecular pathway factors in the supernatant of ELISA cells. ∗P ≤ 0.05, comparison between the miR-29b group and NC-A549 group; #P ≤ 0.05, comparison between the si-FEM1B and NC-NCI-H1792 group.
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