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Abstract
Background and Objective: Chemotherapy and radiotherapy are effective treatment options for cervical cancer (CC), but their efficacy is limited by short survival rate of about 5 years particularly for advance stage CC. Bioinformatics analysis combined with experimental in vivo and in vitro data can identify potential markers of tumorigenesis and cancer progression to improve CC prognosis and survival rate of the patients. This study aims to investigate the prognostic value of family with sequence similarity 83, member A (FAM83A) gene and miR-206 in promoting CC progression and the involved genetic signaling pathways.Method: This was a bioinformatic analysis study based on RNA sequencing data of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and verification by in vivo and in vitro experimental data. It was designed to evaluate whether the aberrantly expressed gene signatures could serve as new potential biomarker to improve prognosis prediction in CC. The TCGA RNA sequencing data [306 cervical squamous cell carcinoma (SCC) and endocervical adenocarcinoma samples and 13 adjacent samples] and GEO data (GSE9750 and GSE52903 datasets) were integrated and performed a bioinformatics analysis.Results: The results showed that CC-associated FAM83A gene serves as a key regulator of CC development and progression. Functionally, we observed that FAM83A is significantly overexpressed in CC, which is linked to poor overall survival as well as disease-free survival in CC patients. The in-vitro and in-vivo assessments performed after silencing FAM83A revealed that cell proliferation was significantly inhibited and the S-phase cell cycle arrest was induced. Mechanistically, FAM83A plays a role in PI3K/AKT signaling, and its downstream molecules could promote CC cell proliferation. Furthermore, functionality assessments by in-vitro luciferase reporter system and immunoblot analysis showed that miR-206 was the upstream of FAM83A and negatively correlated with FAM83A.Conclusion: The miR-206/FAM83A/PI3K/AKT signaling pathway possibly serves as a critical effector in CC progression indicating the potential prognostic value of FAM83A gene as a novel biomarker for CC progression.
Highlights
Background and ObjectiveChemotherapy and radiotherapy are effective treatment options for cervical cancer (CC), but their efficacy is limited by short survival rate of about 5 years for advance stage CC
To determine critical genes involved in the development of CC, the The Cancer Genome Atlas (TCGA) cervical Squamous cell carcinoma (SCC) and Genotype-Tissue Expression (GTEx) RNA sequencing data and a CC gene expression microarray comprising the GSE9750 and GSE52903 datasets were analyzed
We detected the expression of these five up-regulated genes in CC tissues and cells by PCR, and found that FAM83A was most consistent and significant both in tissues and cells
Summary
Background and ObjectiveChemotherapy and radiotherapy are effective treatment options for cervical cancer (CC), but their efficacy is limited by short survival rate of about 5 years for advance stage CC. Bioinformatics analysis combined with experimental in vivo and in vitro data can identify potential markers of tumorigenesis and cancer progression to improve CC prognosis and survival rate of the patients. Prognostic and diagnostic biomarkers play crucial roles in predicting the treatment response, prognosis and disease progression in cancer, developing new therapies, and elucidating tumorigenesis mechanisms [10, 11]. High throughput profiling methods including next-generation sequencing and gene microarray have shown great potentials for identifying reliable prognostic biomarkers for different cancers [12, 13]. Different bioinformatics studies using the datasets of TCGA and Gene Expression Omnibus (GEO) gene microarrays have analyzed the gene sequencing and expression profiles of different tumors and demonstrated that abnormal overexpression or genes are key factors involved in the cancer progression [22, 23]
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