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Ubiquitin E3 Ligase MARCH7 is involved in T cell proliferation and neuronal development. In our previous study, we demonstrated MARCH7 promoted malignant behavior of ovarian cancer via the nuclear factor (NF)-κB and Wnt/β-catenin signaling pathway. However, the expression and function of MARCH7 in cervical cancer remains unknown. The present study aimed to unravel the expression and function of MARCH7 in cervical cancer to elucidate its potential role in the diagnosis and pathogenesis of cervical cancer. Results indicated that the expression of MARCH7 was abnormally high in cervical cancer tissues than normal cervical tissues. However, silencing the expression of MARCH7 in HeLa cells resulted in decreased cell proliferation and invasion. Mechanistic investigations revealed that MARCH7 interacted with VAV2. Silencing the expression of MARCH7 in HeLa cells inhibited the VAV2-RAC1-CDC42 signaling pathway. Overall, the results of the present study identified MARCH7 as a candidate oncogene in cervical cancer, and a potential target for cervical cancer therapy. [ABSTRACT FROM AUTHOR]

Background. Cervical cancer (CC) is one of the most frequent female malignancy. Cancer stem cells (CSCs) positively affect survival outcomes in cancer patients, but in cervical cancer, the mechanism of tumor stem cells is still uncertain. Methods. RNA-seq data and related clinical follow-up of patients suffering from CC were from TCGA. Consensus clustering screened prognostic mRNAsi-related genes and identified molecular subtypes for CC. Based on the overlapping differentially expressed genes (DEGs) in subtypes, we employed LASSO and multivariate Cox regression to screen prognostic-related genes and established the RiskScore system. The patients were grouped by RiskScore, the prognosis was analyzed by the Kaplan-Meier (K-M) curve among the various groups, and the precision of the RiskScore was assessed by the ROC curve. Finally, the potential worth of RiskScore in immunotherapy/chemotherapy response was assessed by evaluating TIDE scores and chemotherapy drug IC 50 values. Results. We noticed that patients with low mRNAsi had a shorter survival and then identified three molecular subtypes (C1-3), with the C1 having the worst prognosis and the lowest mRNAsi. Finally, we identified 7 prognostic-related genes (SPRY4, PPP1R14A, MT1A, DES, SEZ6L2, SLC22A3, and CXCL8) via LASSO and Cox regression analysis. We established a 7-gene model defined RiskScore to predict the prognosis of CC patients. K-M curve indicated that low RiskScore patients had improved prognosis, and ROC curves indicated that RiskScore could precisely direct the prognostic evaluation for those suffering from the cancer. This was also confirmed in the GSE44001 and GSE52903 external cohorts. Patients were more sensitive to immunotherapy if with low RiskScore, and RiskScore exhibited precise assessment ability in predicting response to immunological therapy in CC patients. Conclusion. CC stemness is associated with patient prognosis, and the RiskScore constructed based on stemness characteristics is an independent prognostic index, which is expected to be a guide for immunotherapy, providing a new idea for CC clinical practice. [ABSTRACT FROM AUTHOR]