Search

Chemotherapy is an effective therapeutic modality; nevertheless, a significant proportion of patients diagnosed with lung adenocarcinoma (LUAD) demonstrate resistance to chemotherapy. Therefore, it is crucial to understand the potential regulatory mechanisms to develop novel treatment strategies. This study aims to understand how increased FAM83B expression impacts mitochondrial activity, cell apoptosis, and chemotherapy effectiveness in LUAD. Multiple assays, such as CCK8, wound healing, EdU, and transwell assays, were employed to confirm the augmented chemotherapy resistance, heightened cell proliferation, migration, and invasion caused by FAM83B overexpression in LUAD cells. Furthermore, MIMP, MTG, and ATP assays were utilized to quantify changes in mitochondrial metabolism. In vitro functional assays were performed to evaluate the influence of FAM83B overexpression on the malignant progression and resistance mechanisms to chemotherapy in LUAD. In the context of this study, it was determined that LUAD patients with increased FAM83B expression had shorter survival times, and tissue samples with FAM83B overexpression were more prone to metastasis compared to primary samples. As a result, FAM83B is identified as an adverse prognostic marker. The mechanistic analysis demonstrated that FAM83B impedes the translocation of calbindin 2 (CALB2) from the cytoplasm to the mitochondria, resulting in the inhibition of apoptosis and the promotion of mitochondrial activity. Consequently, this ultimately confers resistance to chemotherapy in LUAD. Furthermore, the administration of metformin, which blocks mitochondrial oxidative phosphorylation (OXPHOS), can restore sensitivity to drug resistance in LUAD. Taken together, these findings provide substantial evidence supporting the notion that FAM83B enhances chemotherapy resistance in LUAD through the upregulation of mitochondrial metabolism and the inhibition of apoptosis. [ABSTRACT FROM AUTHOR]

FAM83B, as one of the FAM83 family members, has been closely involved in cell transformation, and a growing number of scholars have been studied its role in tumours over the years. Whereas the effect and potential mechanism of FAM83B in laryngeal squamous cell carcinoma (LSCC) have not been investigated. In this research, we discovered that the expression quantity of FAM83B was remarkably higher in LSCC tissues (79.65 ± 35.98) than in matched adjacent tissues (59.34 ± 32.59) by tissue microarrays and immunohistochemistry. Furthermore, expression of FAM83B was knocked down in HEP-2 and TU177 cell lines via lentivirus, and in the course of intracorporal and extracorporeal experiments, FAM83B knockdown showed the inhibition of tumour growth, migration, and invasion ability. Moreover, cell cycle assay showed that FAM83B knockdown leads to an apparent accumulation of cells in the G1 phase, indicating that FAM83B knockdown can inhibit cell proliferation. Meanwhile, western blotting (WB) demonstrated that FAM83B knockdown led to a significant reduction in CDK4/CDK6/CCND1 protein expression, which may have decelerated cell cycle progression. Collectively, this study demonstrates that FAM83B serves as an oncogene in LSCC, promoting cell proliferation by controlling the protein expression of CDK4, CDK6, and CCND1, thus inducing a transference of the G1 stage to S stage in cell-cycle of LSCC cells. These results provide an academic foundation for elucidating the mechanism of LSCC occurrence and evolution and for developing treatment strategies for LSCC.

Abstract Objects The family with sequence similarity 83B (FAM83B) is one of the markers for poor prognosis in several carcinomas, but the expression and the mechanism resulted in malignant phenotype in lung adenocarcinoma (LUAD) remain to be elucidated. Methods Data of RNA-seq in LUAD were downloaded from the cancer genome atlas (TCGA) database for differential expression and survival analysis, and immunohistochemistry was employed to analyze the protein expression of FAM83B in 126 cases of primary LUAD. The LUAD cell lines were collected for the detection of the effects on migration and invasion. Then, western blot was performed to measure the expression of tissue inhibitor of metalloproteinase (TIMP)-1 and activation of PI3K/AKT/NF-κB pathway. Results FAM83B was overexpressed in multiple types of carcinomas; The differential expression analysis revealed that the level of FAM83B was higher in LUAD than that in para-carcinoma; The patients with overexpression of FAM83B were with shorter overall survival (OS), disease specific survival (DSS) and progress free interval (PFI); Enrichment analysis suggested it was related to the focal adhesion of LUAD. Immunohistochemistry analysis demonstrated that higher FAM83B expression was positively related to lymph node metastasis in primary. Scratch assay and Borden chamber assay showed that the overexpression of FAM83B promoted migration and invasion activity in vitro. Furthermore, high level of FAM83B accelerated the tumorigenesis in vivo. Western blot showed that TIMP-1 was upregulated in H1299/FAM83B OE cells accompanying by the activation of PI3K/AKT/NF-κB pathway. Conclusions FAM83B was a marker for poor prognosis of LUAD and it might promote the expression of TIMP-1 by activating PI3K/AKT/NF-κB pathway and then affect the ECM balance, which resulted in the migration and invasion of LUAD.

Objects: The family with sequence similarity 83B (FAM83B) is one of the markers for poor prognosis in several carcinomas, but the expression and the mechanism resulted in malignant phenotype in lung adenocarcinoma (LUAD) remain to be elucidated. Methods: Data of RNA-seq in LUAD were downloaded from the cancer genome atlas (TCGA) database for differential expression and survival analysis, and immunohistochemistry was employed to analyze the protein expression of FAM83B in 126 cases of primary LUAD. The LUAD cell lines were collected for the detection of the effects on migration and invasion. Then, western blot was performed to measure the expression of tissue inhibitor of metalloproteinase (TIMP)-1 and activation of PI3K/AKT/NF-κB pathway. Results: FAM83B was overexpressed in multiple types of carcinomas; The differential expression analysis revealed that the level of FAM83B was higher in LUAD than that in para-carcinoma; The patients with overexpression of FAM83B were with shorter overall survival (OS), disease specific survival (DSS) and progress free interval (PFI); Enrichment analysis suggested it was related to the focal adhesion of LUAD. Immunohistochemistry analysis demonstrated that higher FAM83B expression was positively related to lymph node metastasis in primary. Scratch assay and Borden chamber assay showed that the overexpression of FAM83B promoted migration and invasion activity in vitro. Furthermore, high level of FAM83B accelerated the tumorigenesis in vivo. Western blot showed that TIMP-1 was upregulated in H1299/FAM83B OE cells accompanying by the activation of PI3K/AKT/NF-κB pathway. Conclusions: FAM83B was a marker for poor prognosis of LUAD and it might promote the expression of TIMP-1 by activating PI3K/AKT/NF-κB pathway and then affect the ECM balance, which resulted in the migration and invasion of LUAD. [ABSTRACT FROM AUTHOR]

FAM83B, as one of the FAM83 family members, has been closely involved in cell transformation, and a growing number of scholars have been studied its role in tumours over the years. Whereas the effect and potential mechanism of FAM83B in laryngeal squamous cell carcinoma (LSCC) have not been investigated. In this research, we discovered that the expression quantity of FAM83B was remarkably higher in LSCC tissues (79.65 ± 35.98) than in matched adjacent tissues (59.34 ± 32.59) by tissue microarrays and immunohistochemistry. Furthermore, expression of FAM83B was knocked down in HEP-2 and TU177 cell lines via lentivirus, and in the course of intracorporal and extracorporeal experiments, FAM83B knockdown showed the inhibition of tumour growth, migration, and invasion ability. Moreover, cell cycle assay showed that FAM83B knockdown leads to an apparent accumulation of cells in the G1 phase, indicating that FAM83B knockdown can inhibit cell proliferation. Meanwhile, western blotting (WB) demonstrated that FAM83B knockdown led to a significant reduction in CDK4/CDK6/CCND1 protein expression, which may have decelerated cell cycle progression. Collectively, this study demonstrates that FAM83B serves as an oncogene in LSCC, promoting cell proliferation by controlling the protein expression of CDK4, CDK6, and CCND1, thus inducing a transference of the G1 stage to S stage in cell-cycle of LSCC cells. These results provide an academic foundation for elucidating the mechanism of LSCC occurrence and evolution and for developing treatment strategies for LSCC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Despite the progress made in targeted anticancer therapies in recent years, challenges remain. The identification of new potential targets will ensure that the arsenal of cancer therapies continues to expand. FAM83B was recently discovered in a forward genetic screen for novel oncogenes that drive human mammary epithelial cell (HMEC) transformation. We report here that elevated FAM83B expression increases Phospholipase D (PLD) activity, and that suppression of PLD1 activity prevents FAM83B-mediated transformation. The increased PLD activity is engaged by hyperactivation of epidermal growth factor receptor (EGFR), which is regulated by an interaction involving FAM83B and EGFR. Preventing the FAM83B/EGFR Interaction by site-directed mutation of lysine 230 of FAM83B suppressed PLD activity and MAPK signaling. Furthermore, ablation of FAM83B expression from breast cancer cells inhibited EGFR phosphorylation and suppressed cell proliferation. We propose that understanding the mechanism of FAM83Bmediated transformation will provide a foundation for future therapies aimed at targeting its function as an intermediary in EGFR, MAPK and mTOR activation. [ABSTRACT FROM AUTHOR]

Our previous study demonstrated the role of family with sequence similarity 83, member B (FAM83B) in endometrial cancer tumorigenesis and metastasis. FAM83B is involved in epithelial-to-mesenchymal transition (EMT). However, the regulatory network of EMT, which promotes endometrial cancer cell metastasis, involving microRNAs (miRNAs/miRs) and FAM83B, has not been elucidated. To investigate the potential mechanism underlying miR-199a/b-5p in endometrial cancer, the effect of miR-199a/b-5p and its targeted FAM83B gene on the biological behaviour of endometrial cancer cells was assessed. The Gene Expression Omnibus dataset analysis results revealed that the expression levels of 150 miRNAs in non-cancerous endometrial tissues were upregulated compared with those in endometrial cancer tissues. TargetScan predicted that the nucleotides 672–679 of FAM83B 3′-untranslated region (UTR) were the target sites of miR-199a/b-5p. The differentially expressed miRNAs were enriched in several Kyoto Encyclopedia of Genes and Genomes pathways. Reverse transcription-quantitative PCR analysis revealed that the expression levels of miR-199a/b-5p in the endometrial non-cancerous cell lines were significantly upregulated compared with those in the six endometrial cancer cell lines. miR-199a/b-5p inhibited the EMT signaling pathway by regulating the expression levels of E-cadherin, N-cadherin, Snail, α-smooth muscle actin, vimentin and Twist. This suggested that miR-199a/b-5p inhibited endometrial cancer cell proliferation and migration through the inhibition of the EMT signaling pathway. Furthermore, the nucleotides 672–679 of the FAM83B 3′-UTR were demonstrated to be the binding site of miR-199a/b-5p. These results suggested that miR-199a/b-5p inhibited endometrial cancer cell proliferation and metastasis by targeting the 3′-UTR of FAM83B, which is involved in the EMT signaling pathway. [ABSTRACT FROM AUTHOR]

• FAM83B was upregulated in endometrial cancer tissues and cell lines. • FAM83B expression was correlated with FIGO stage and myometrial invasion. • FAM83B knockdown inhibited endometrial cancer cell proliferation and cell cycle. • FAM83B knockdown inhibited endometrial cancer cell migration and invasion. • FAM83B knockdown silenced the PI3K/AKT/mTOR pathway and promoted autophagy. Family with sequence similarity 83 member B (FAM83B) has been recently identified as an oncogene involved in the development of various human cancers. However, the role of FAM83B in endometrial cancer tumorigenesis and metastasis is unclear. In this study, we found that the expression of FAM83B was upregulated in endometrial cancer tissues and cell lines. FAM83B expression in endometrial cancer tissues was significantly higher than that in normal tissues and higher FAM83B expression was closely related to poorly survival rate according to TCGA analysis. Moreover, FAM83B expression was correlated with International Federation of Gynecology and Obstetrics (FIGO)stage and myometrial invasion but had no significant correlation with age or histological grade. FAM83B knockdown inhibited endometrial cancer cell proliferation, migration, and invasion arrested the cell cycle at the G1/S stage and promoted apoptosis. FAM83B knockdown also inhibited endometrial cancer growth and lung metastasis in vivo. FAM83B knockdown silenced the PI3K/AKT/mTOR pathway and promoted autophagy. Furthermore, activation of the PI3K/AKT/mTOR pathway reversed FAM83B knockdown-induced autophagy promotion and inhibition of proliferation, migration, and invasion in endometrial cancer cells. Taken together, these results indicate that FAM83B promotes endometrial cancer cell proliferation and metastasis by inhibiting autophagy via activating the PI3K/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

Although targeted therapy has improved the survival rates in the last decade, non-small-cell lung cancer (NSCLC) is still the most common cause of cancer-related death. The challenge of identifying new targets for further effective therapies still remains. The FAMily with sequence similarity 83 (FAM83) members have recently been described as novel oncogenes in numerous human cancer specimens and shown to be involved in epidermal growth factor receptor (EGFR) signaling. Here, gene expression of FAM83A and B was analyzed in a cohort of 362 NSCLC patients using qPCR. We further investigated relations in expression and their prognostic value. Functional assays in NSCLC cell lines were performed to evaluate FAM83A and B involvement in proliferation, anchorage-independent growth, migration, and the EGFR pathway. We observed a highly increased gene expression level of FAM83A (ø = 68-fold) and FAM83B (ø = 20-fold) which resulted in poor survival prognosis (p < 0.0001 and p = 0.002). Their expression was influenced by EGFR levels, pathway signaling, and mutation status. Both genes affected cell proliferation, and FAM83A depletion resulted in reduced migration and anchorage-independent growth. The results support the hypothesis that FAM83A and B have different functions in different histological subtypes of NSCLC and might be new therapeutic targets. [ABSTRACT FROM AUTHOR]

FAM83B (family with sequence similarity 83, member B) seems to emerge as a new class of players involved in the development of a variety of malignant tumors. Yet the molecular mechanisms are not well understood. The present study is intended to investigate the expression and function of FAM83B in pancreatic ductal adenocarcinoma (PDAC). In this study, we found that the expression of FAM83B was significantly increased both in PDAC cell lines and PDAC tumor tissues. FAM83B expression was positively related with advanced clinical stage and poor vital status. Higher FAM83B expression predicted shorter overall survival in PDAC patients, regardless of lymphatic metastasis status and histological differentiation. Actually, FAM83B may act as an independent prognostic indicator as well. What's more, down-regulation of FAM83B in PDAC cells contributed to G0/G1 phase arrest and inhibition of cell proliferation. Finally, a subcutaneous xenograft model indicated that knockdown of FAM83B significantly reduced the tumor volume in vivo . Our findings have provided supporting evidence for the potential molecular biomarker role of FAM83B in PDAC. It's of great interest and broad significance to target FAM83B in PDAC, which may conduce to develop a meaningful and effective strategy in the diagnosis and treatment of PDAC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.