FAM83A as a Potential Biological Marker Is Regulated by miR-206 to Promote Cervical Cancer Progression Through PI3K/AKT/mTOR Pathway

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.

FAM83A Promotes the Proliferative and Invasive Abilities of Cervical Cancer Cells via Epithelial-Mesenchymal Transition and the Wnt Signaling Pathway

“…Rong et al also indicated that FAM83A is regulated by miR-206 and promotes cervical cancer progression through the PI3K/AKT/mTOR pathway [13]. Liu et al proposed that FAM83A is involved in the occurrence and development of lung cancer and is related to poor prognosis [29].…”

“…FAM83A promotes tumor progression and increases proliferation, invasion, drug resistance, and stem cell-like traits in breast, lung, hepatocellular, and pancreatic cancers [5,[9][10][11][12]. A recent study indicated that FAM83A is regulated by miR-206 to promote cervical cancer development via the PI3K/AKT/ mTOR pathway [13]. Xu et al also reported that FAM83A was associated with cervical lesion progression and carcinogenesis and that it was specific for cervical cancer as opposed to cervical intraepithelial neoplasia (CIN) 2 to CIN 3 and normal cervical epithelium [14].…”

Aberrant epigenetic and transcriptional events associated with breast cancer risk

“…It was identified based on its transforming potential (35)(36)(37). FAM83A upregulation has been detected in multiple human tumor types, including breast, lung, pancreatic and cervical cancer (37)(38)(39)(40)(41)(42)(43)(44). Lee et al (45,46) revealed the ability of FAM83A to confer resistance to epidermal growth factor receptor/ tyrosine kinase inhibitors (EGFR-TKIs) through interactions with c-RAF and PI3K p85 in breast cancer.…”

Comprehensive Analysis of Prognostic Significance and Immune Infiltration for FAM83 Family in Cervical Cancer

“…The above research showed that the high expression of FAM83A/B/H in cervical cancer had important value in the occurrence, development, and prognosis evaluation of cervical cancer. In recent years, many studies have shown that FAM83A/B/H can activate MAPK, Wnt, and PI3K/AKT/mTOR signaling pathways in lung and pancreatic cancers [13,30,[34][35][36][37][61][62][63] and regulate tumor occurrence, development, and biological behavior. In order to better clarify the molecular mechanism, biological function, and related signal regulation network of FAM83A/B/H in cervical cancer, GO enrichment analysis on FAM83A/B/H and their closely related genes was performed, which revealed that the above genes were involved in the formation of cell-substrate junction, membrane raft, desmosome, and regulated various biological behaviors, including lipid binding, cadherin, and calcium-dependent protein binding, and regulating skin and epidermis development, in ammatory response and cell junction organization.…”