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. 2025 Jun 10;16(1):1050.
doi: 10.1007/s12672-025-02896-3.

LncRNA MIR99AHG serves as a diagnostic marker for early lung cancer and regulates cancer cell growth and metastasis via miR-194-5p

Wenhui Li #  1 , Wenhan Li #  2 , Zhen Xu  3
Affiliations

LncRNA MIR99AHG serves as a diagnostic marker for early lung cancer and regulates cancer cell growth and metastasis via miR-194-5p

Wenhui Li et al. Discov Oncol. .

Abstract

Background: Lung cancer ranks among the foremost causes of mortality associated with cancer. Non-small cell lung cancer (NSCLC) represents the predominant subtype, and the survival rate is suboptimal.

Objectives: This study investigated the clinical relationship between MIR99AHG and NSCLC, as well as elucidated the potential mechanisms. This study identified novel molecular targets for NSCLC.

Patients and methods: This study involved 119 NSCLC patients and 105 benign lung lesions patients. qPCR was employed to assess the expression of MIR99AHG and miR-194-5p. The clinical correlation, diagnostic value, and predictive capacity of MIR99AHG were evaluated utilizing chi-square tests, ROC analysis, and logistic regression models, respectively. A cell model exhibiting overexpression of MIR99AHG was established, and the impact of MIR99AHG overexpression, and in conjunction with miR-194-5p overexpression, on the functional characteristics of lung cancer cells was investigated through CCK-8 and Transwell assays.

Results: MIR99AHG exhibited down-regulation in NSCLC patients' serum and lung cancer cell lines, while miR-194-5p showed up-regulation. The expression of MIR99AHG was correlated with TNM staging and LNM status in early-stage NSCLC patients. MIR99AHG demonstrated predictive capabilities for the early NSCLC occurrence, both independently and in conjunction with serum tumor markers, and exhibited significant diagnostic potential for this condition. Moreover, the overexpression of MIR99AHG could inhibit the proliferation, migration, and invasion of lung cancer cells. However, the concurrent overexpression of MIR99AHG and miR-194-5p appeared to negate this inhibitory effect.

Conclusion: MIR99AHG might as a supplementary diagnosis tool for early NSCLC. Furthermore, MIR99AHG could regulate the initiation and advancement of NSCLC via miR-194-5p.

Keywords: Cell function; Diagnosis; LncRNA; Non-small cell lung carcinoma; miRNA.

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Conflict of interest statement

Declarations. Competing interests: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: The study has received approval from the Ethics Committee of Tengzhou Central People’s Hospital, and all experimental protocols have undergone ethical review. This research is conducted in strict accordance with the ethical guidelines outlined in the Helsinki Declaration established by the World Medical Association, as well as the Ethical Review Measures for Biomedical Research Involving Human Subjects set forth by the National Health Commission. Consent to participate: All participants have provided written informed consent, and the research protocol has thoroughly elucidated their rights, potential risks, and the objectives of the study. Each participant has consented to engage in this research and to the publication of pertinent data. Consent to publish: Not applicable.

Figures

Fig. 1
Fig. 1
The lncRNA MIR99AHG levels in patients in UALCAN database. A the levels in normal and LUAD tumor tissue. B the levels in LUAD patients with different TNM stages. C the levels in normal and LUSC tumor tissue. D the levels in LUSC patients with different TNM stages
Fig. 2
Fig. 2
The relative expression levels of lncRNA MIR99AHG of serum and cell lines in NSCLC patients. A the levels of serum in control and NSCLC group. B the levels in NSCLC patients with different TNM stages. C the levels in NSCLC patients with different LNM status. D, the levels in normal cell line (BEAS-2B), as well as lung cancer cell lines (A549, CAL-12T, H1299, H1975, and PC-9). **P < 0.01; ***P < 0.001 vs. control/stage I/LNM negative
Fig. 3
Fig. 3
The diagnostic values of serum lncRNA MIR99AHG and tumor markers in patients with NSCLC. A The independent diagnostic efficacy of serum markers (AFP, CEA, NSE, and CYFRA21-1). B The independent diagnostic efficacy of serum MIR99AHG. C, the combined diagnostic efficacy of serum MIR99AHG and markers
Fig. 4
Fig. 4
The effects of lncRNA MIR99AHG overexpression on gene expression and cell functions. A the MIR99AHG levels in A549 and H1299 cells. B the proliferative activity of A549 cells. C The proliferative activity of H1299 cells. D the migration ability of cells. E the invasion ability of cells. ***P < 0.001 vs. control
Fig. 5
Fig. 5
The relationship between lncRNA MIR99AHG and miR-194-5p. A The binding sites of MIR99AHG and miR-194-5p. B The luciferase activity of WT-MIR99AHG and MUT-MIR99AHG in A549 cells. C The luciferase activity of WT-MIR99AHG and MUT-MIR99AHG in H1299 cells. D The serum miR-194-5p levels in control and NSCLC group. E The correlation between MIR99AHG and miR-194-5p. F The miR-194-5p levels in normal cell line (BEAS-2B), as well as lung cancer cell lines (A549, CAL-12T, H1299, H1975, and PC-9). **P < 0.01; ***P < 0.001 vs. control/BEAS-2B
Fig. 6
Fig. 6
The effects of lncRNA MIR99AHG and miR-194-5p simultaneous overexpression on gene expression and cell functions. A, the miR-194-5p levels in A549 and H1299 cells. B, the proliferative activity of A549 cells. C, the proliferative activity of H1299 cells. D, the migration ability of cells. E, the invasion ability of cells. ***P < 0.001 vs. control. ##P < 0.01; ###P < 0.001 vs. oe- MIR99AHG
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