FAM83A is amplified and promotes tumorigenicity in non-small cell lung cancer via ERK and PI3K/Akt/mTOR pathways

Hu, Haiyang; Wang, Fajiu; Wang, Muyun; Liu, Yuanyuan; Wu, Han; Chen, Xi; Lin, Qiang

doi:10.7150/ijms.33992

Cited by 28 publications

(42 citation statements)

References 29 publications

(37 reference statements)

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“…This signaling pathway is mediated through serine and/or threonine phosphorylation of different types of downstream compounds, of them PI3K and AKT are the main proteins. The effects of FAM83A on PI3K/AKT pathway have been investigated in few cancers (22,(35)(36)(37). Liu et al analyzed TCGA database and reported that FAM83A is overexpressed in hepatocellular carcinoma (HCC) cells and plays a cancer-promoting and treatmentresistance role.…”

Section: Discussionmentioning

confidence: 99%

“…Hu et al examined the roles and possible mechanism of FAM83A in non-small cell lung cancer (NSCLC) progression through bioinformatics analysis of GEO and TCGA databases and RT-PCR and reported high FAM83A expression in NSCLC that was associated with the poor prognosis (35). In vitro model showed that silencing FAM83A by siRNA/shRNA markedly reduced cell proliferation, induced cell apoptosis, and inhibited cell motility.…”

Section: Discussionmentioning

confidence: 99%

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

Zhaodong

et al. 2020

Front. Med.

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Zhaodong

et al. 2020

Front. Med.

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“…Another study has shown that AKR1B10 can promote proliferation and migration/invasion of breast cancer cells via the ERK and FAK/Src/Rac1 signaling pathway [8,32]. Several studies have also demonstrated that PI3K/AKT and MEK/ERK signaling pathways can be activated in tumors together [33][34][35]. AKR1B10 may affect several signaling pathways in BC.…”

Section: Discussionmentioning

confidence: 99%

AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway

et al. 2020

Preprint

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BackgroudAberrant expression of Aldo-Keto reductase family 1 member B10 (AKR1B10) has been observed during the progression of some human carcinomas. However, the expression pattern and clinical relevance of AKR1B10 in breast cancer (BC) need clarification.MethodsThe relationship between the high expression of AKR1B10 and the overall prognosis and disease-free survival of breast cancer patients was analyzed by Kaplan-Meier Plotter database. Breast cancer cell lines MCF-7/AKR1B10 stably overexpressing AKR1B10 and breast cancer cell lines BT-20/shAKR1B10 that knock down AKR1B10 were constructed, respectively. RT-qPCR, Western blot and immunohistochemistry were used to detect the expression of AKR1B10 in breast cancer and its normal tissues. CCK8 cell proliferation assay and cell scratch test were used to detect the proliferation and migration of breast cancer cells. Western blot was used to detect the expression of proliferation-related proteins cyclinD1, c-myc, survivin and EMT-related proteins twist, snail, slug, ZEB1, E-cadherin, PI3K, p-PI3K, AKT, p-AKT, IKBα, p-IKBα, NF-κB p65, and p-NF-κB p65 proteins in breast cancer cells. The PI3K inhibitor LY94002 was used to treat MCF-7 cells to detect PI3K/AKT/NF-κB signal cascade protein Expression, and expression of NF-κB p65 in nucleoproteins and plasma proteins.ResultsIn this study, we found that AKR1B10 expression was higher in BC tissue compared to paired non-cancerous tissue. The expression of AKR1B10 positively correlated with lymph node metastasis, tumor size, Ki67 expression, and p53 expression, but inversely correlated with overall and disease-free survival rates. Gene Ontology (GO) analysis showed that AKR1B10 was closely related to cell proliferation. Overexpression of AKR1B10 facilitated proliferation and migration of BC cells in vitro in association with induction of epithelial-mesenchymal transition. Conversely, knockdown of AKR1B10 inhibited these effects. Mechanistically, silencing AKR1B10 reduced the phosphorylation of PI3K, AKT, and NF-κB p65, whereas AKR1B10 overexpression activated these signaling molecules. Indeed, PI3K inhibition attenuated NF-κB p65 nuclear localization.ConclusionsOur results demonstrate that AKR1B10 promotes proliferation and migration of BC cells and represents a novel prognostic indicator as well as a potential therapeutic target in BC.

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“…promotes lung cancer progression by regulating the Wnt and Hippo signaling pathways. Hu HY et al found that FAM83A promotes tumorigenesis of NSCLC at least partly via ERK and PI3K/Akt/mTOR pathways, making it a promising therapeutic target (13) . Zhou FR et al (19) found that co-expression of FAM83A and PD-L1 in tumor cells was a credible biomarker predictor for worse survival in resected LAC patients.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, increasing studies have found that dysregulated FAM83A is a potential biomarker in various cancers, including breast, hepatocellular and lung adenocarcinoma cancers (7; 8; 9; 10; 11; 12) . It was reported that FAM83A promotes lung adenocarcinoma cancer progression by regulating the Wnt and Hippo (8) and ERK and PI3K/Akt/mTOR pathways (13) , making it a promising therapeutic target. Besides, circ-ZKSCAN1/miR-330-5p/FAM83A feedback loop plays important role in promoting the progress of NSCLC (14) .…”

Section: Introductionmentioning

confidence: 99%

Family With Sequence Similarity 83, Member A (FAM83A) As a Promising Prognostic Biomarker in Lung Squamous Cell Cancer

Wang¹,

Lu²,

Feng³

et al. 2020

Preprint

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Background: Increasing studies have found the dysregulated FAM83A as a potential biomarker in various cancers. Its function in cancer cells is largely unknown, and especially their role in LUSC remains unclear. We detected the expression level and prognosis role of FAM83A in LUSC.Methods: The bioinformatics methods were performed initially to predict the expression level and prognostic value of FAM83A mRNA in LUSC. We used IHC to examine its protein expression level and identify its prognostic value using 132 pairs of tissues.Results: Results from TCGA and Oncomine databases revealed that FAM83A mRNA expression level was significantly higher in LUSC than that in normal lung tissue. TCGA and GEO databases revealed FAM83A mRNA overexpression was significantly associated with poorer OS of LUSC patients (all P<0.05). Furtherly, our IHC results revealed that FAM83A was overexpressed in 78 (59.1%) patients and 19(14.4%) pancancerous tissues (P<0.001). Kaplan-Meier analyses revealed that high FAM83A protein expression was significantly associated with decreased 5-years’ OS (P = 0.007) and PFS (P = 0.007). Via multivariate analysis, FAM83A expression level was independent prognostic factor for both OS (P = 0.006) and PFS (P = 0.002).Conclusion: FAM83A was overexpressed in LUSC and it could serve as a prognosis prediction biomarker for LUSC. FAM83A could act as one new potential therapeutic target for LUSC treatment.

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FAM83A is amplified and promotes tumorigenicity in non-small cell lung cancer via ERK and PI3K/Akt/mTOR pathways

Cited by 28 publications

References 29 publications

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

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

AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway

Family With Sequence Similarity 83, Member A (FAM83A) As a Promising Prognostic Biomarker in Lung Squamous Cell Cancer

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