SNHG3/hsa-miR-455-5p Axis-mediated High Expression of MTHFD2 Correlates with Tumor Immune Infiltration and Endometrial Carcinoma Progression

Sa Wu; Weisong Cai; Yanli Li; Wenfu Tan; Yichong Yuan; Zhigang Zhou; Jie Shi; Xiaotian Liu; Han Gao

doi:10.7150/ijms.81962

SNHG3/hsa-miR-455-5p Axis-mediated High Expression of MTHFD2 Correlates with Tumor Immune Infiltration and Endometrial Carcinoma Progression

Int J Med Sci. 2023 Jul 3;20(8):1097-1113. doi: 10.7150/ijms.81962. eCollection 2023.

Authors

Sa Wu¹, Weisong Cai², Yanli Li¹, Wenfu Tan¹, Yichong Yuan¹, Zhigang Zhou¹, Jie Shi¹, Xiaotian Liu¹, Han Gao¹

Affiliations

¹ Department of Gynaecology Ⅱ, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Abstract

Purpose: Endometrial carcinoma (EC) is one of the three most common female genital tract cancers, and it contributes to the leading deaths of gynecologic cancer. MTHFD2 was reported up-regulated and associated with poor prognosis in many malignancies. However, its biological functions and mechanisms in EC are unclear. The present study aimed to identify the biological functions and potential molecular mechanisms of MTHFD2 in EC. Methods: The gene expression and information of patients used in this study were derived from TCGA, GEO and HPA databases. KM survival analysis was used to explore the clinical outcomes of EC patients and correlation analysis was applied to find the correction between MTHFD2 expression level and immune infiltration in EC. We used GO and GSEA analysis to explore the biological functions and mechanisms of MTHFD2. The CCK8 assay, the colony formation assay and the transwell migration assay were conducted to validate the function of MTHFD2 in EC cells. We applied STRING to find the protein that interacted with MTHFD2. Finally, ENCORI was used to explore the potential upstream regulation of MTHFD2 in EC and it was validated in EC cells. Results: In the present study, we found that MTHFD2 was up-regulated in EC and its high expression level was associated with patients' poor prognosis and adverse clinical parameters. MTHFD2 level was shown to be correlated with immune infiltration. Knockdown of MTHFD2 inhibited the malignant phenotype of HEC-1A and Ishikawa cells, including proliferation, colony formation and migration. Furthermore, we found the SNHG3/hsa-miR-455-5p axis as the potential upstream of MTHFD2. Conclusion: SNHG3/hsa-miR-455-5p axis-mediated high expression of MTHFD2, and the MTHFD2 expression level was associated with tumor immune infiltration and endometrial carcinoma progression. Knockdown of MTHFD2 significantly inhibited the malignant phenotype of EC cells. MTHFD2 may be a valuable predictive biomarker, and targeting MTHFD2 may be an effective way to improve the therapeutic effect in EC.

Keywords: MTHFD2; biomarker; endometrial carcinoma; lncRNAs; prognosis.

MeSH terms

Cell Line, Tumor
Endometrial Neoplasms* / genetics
Endometrial Neoplasms* / pathology
Female
Humans
MicroRNAs* / genetics
MicroRNAs* / metabolism

Substances

MicroRNAs
MIRN455 microRNA, human
MTHFD2 protein, human