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LncRNA MAFG-AS1 Promotes Lung Adenocarcinoma Cell Migration and Invasion by Targeting miR-3196 and Regulating SOX12 Expression

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Abstract

Lung adenocarcinoma (LUAD) patients exhibit poor prognosis, primarily due to metastasis. Emerging studies have demonstrated that long noncoding RNAs (lncRNAs) play critical roles in cancer progression and metastasis besides their physiological function. Here, we investigated the potential role of lncRNA MAF BZIP Transcription Factor G Antisense RNA 1 (MAFG-AS1) in LUAD metastasis by analyzing its expression in The Cancer Genome Atlas (TCGA) LUAD database, and its function in LUAD using in vitro and in vivo experiments. We performed bioinformatics analysis, western blotting, dual-luciferase reporter gene assay, RNA immunoprecipitation (RIP), and rescue assays to reveal the molecular mechanisms underlying MAFG-AS1 function. We observed augmented expression of MAFG-AS1 in LUAD tissues compared with normal adjacent tissues, and its association with poor prognosis. Furthermore, MAFG-AS1 overexpression promoted LUAD cell migration, proliferation, invasion, and epithelial mesenchymal transition (EMT). Besides, MAFG-AS1 also targeted miR-3196 directly by acting as an endogenous sponge, thereby rescuing the inhibition of SOX12, a target of miR-3196. Thus, the rescue assays demonstrated that MAFG-AS1 promotes cell migration, invasion, and EMT by modulating the miR-3196/SOX12 pathway. In conclusion, our findings suggest that MAFG-AS1/miR-3196/SOX12 axis regulates LUAD progression and is a potential therapeutic target for LUAD.

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Data Availability

Datasets used and analyzed during this study are available from the corresponding author upon reasonable request.

Abbreviations

LUAD:

Lung adenocarcinoma

TCGA:

The cancer genome atlas

lncRNAs:

Long noncoding RNA

EMT:

Epithelial-mesenchymal transition

FBS:

Fetal bovine serum

qRT-PCR:

Quantitative real-time polymerase chain reaction

EdU:

5-Ethynyl-2′-deoxyuridine

FISH:

Fluorescent in situ hybridization

RIP:

RNA immunoprecipitation

ceRNAs:

Competing endogenous RNAs

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Authors and Affiliations

  1. Department of Respiratory, Quzhou People’s Hospital Affiliated to Wenzhou Medical University, No.2, zhongloudi, Kecheng District, Quzhou, 324000, Zhejiang, China

    Qian Wu & Jianyang Jiang

Authors
  1. Qian Wu
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  2. Jianyang Jiang
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Contributions

QW performed the experiments, generated data, and data analysis and interpretation of data. JJ made substantial contributions to the conception and design of the present study. All authors contribute to the drafting and revision of the manuscript. All authors read, revised and approved the manuscript and agreed to be accountable for all aspects of the research in ensuring that the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Jianyang Jiang.

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Conflict of interest

The authors declare that they have no known competing financial interest or personal relationships that could influence the results reported in this manuscript.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Quzhou People’s Hospital Affiliated to Wenzhou Medical University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Animal studies were carried out in accordance with the National Institute of Health’s Guide for the Care and Use of Laboratory Animals, with the approval of the Animal Research Committee of Quzhou People’s Hospital Affiliated to Wenzhou Medical University.

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All patients provided written informed consent.

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Supplementary Information

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12033_2022_455_MOESM1_ESM.tif

Supplementary Figure 1. miR-3196 mimics inhibits cell migration and invasion of LUAD cells. (A) Wound healing assay was used to determine the effect of miR-3196 mimics on cell migration. (B) Transwell assay was used to examine cell invasion. *P<0.05 and **P<0.01 (TIF 26154 kb)

Table S1. The miRNAs that bind to MAFG-AS1 is predicted by starBase (XLSX 12 kb)

Table S2. The miRNAs that bind to MAFG-AS1 is predicted by miRDB (XLSX 11 kb)

Table S3. The target gene of miR-3196 is predicted by miRDB (XLSX 21 kb)

12033_2022_455_MOESM5_ESM.xlsx

Table S4. The mRNAs are found to be positively correlated with the expression of lncRNA MAFG-AS1 (Spearman's Correlation>0.3) in the TCGA database (XLSX 1263 kb)

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Wu, Q., Jiang, J. LncRNA MAFG-AS1 Promotes Lung Adenocarcinoma Cell Migration and Invasion by Targeting miR-3196 and Regulating SOX12 Expression. Mol Biotechnol 64, 970–983 (2022). https://doi.org/10.1007/s12033-022-00455-7

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  • DOI: https://doi.org/10.1007/s12033-022-00455-7

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