FAM122A supports the growth of hepatocellular carcinoma cells and its deletion enhances Doxorubicin-induced cytotoxicity

Zhou, Yong; Shi, Wen-Yang; He, Wei; Yan, Zhao-Wen; Liu, Man-Hua; Chen, Jing; Yang, Yunsheng; Wang, Yin-Qi; Chen, Guoqiang; Huang, Ying

doi:10.1016/j.yexcr.2019.111714

Cited by 13 publications

(7 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GSEA analysis revealed that the T extreme group was primarily enriched with the gene signatures related to tumor growth and tumor immunoreaction such as “signaling pathways regulating pluripotency of stem cells,” “Wnt signaling pathway,” and “TGF‐beta signaling pathway” (Figure 2A ), which was consistent with the prognostic result. Meanwhile, WGCNA analysis based on global circRNA abundance in tumor identified a gene module related to CRI (MEgreen, p = 0.01), including well‐known HCC‐related genes such as CXCL13, [ 31 ] FAM122C, [ 32 ] and CELF2. [ 33 ] Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the module showed that genes were significantly enriched in immune regulatory pathways, indicating a potential relationship between global circRNA abundance and immune regulation (Figure 2C ).…”

Section: Resultsmentioning

confidence: 99%

Dysregulation of global circular RNA abundance regulated by spliceosomes predicts prognosis in hepatocellular carcinoma

Qiu

Chen

et al. 2022

Hepatol Commun

View full text Add to dashboard Cite

CircRNAs have been reported to play crucial roles in tumor progression and recurrence, showing potential as biomarkers in cancer. However, the global abundance of circRNA and their involvement in hepatocellular carcinoma (HCC) development have not been fully explored. Whole transcriptome sequencing was performed on tumor and peritumor from 60 patients with HCC to quantify the expression of circRNAs, and the global circRNA abundance was calculated by circRNA index (CRI). Gene‐set enrichment analysis and weighted gene co‐expression network analysis were used to reveal the biological signaling pathways associated with the global circRNA abundance. The correlation between the global circRNA abundance and the infiltration level of CD8+ T cells was explored by immunohistochemical assays. Small interfering RNA was used to knock down the pre–messenger RNA spliceosome in HCC cell lines to verify the regulation of spliceosome in global circRNA abundance. We found that dysregulation of global circRNA abundance in both tumor and peritumor could lead to worse prognosis. The immunohistochemical assay further revealed that the dysregulation of global circRNA abundance in both tumor and peritumor would obstruct the CD8+ T cells from invading into the tumor, which might explain its correlation with HCC prognosis. We also demonstrated that the spliceosome genes were the main factors to regulate the global circRNA abundance in HCC, and these results were also confirmed by knockdown experiments. Conclusion: This study revealed the association between the global circRNA abundance and patients' prognosis and its underlying mechanism.

show abstract

Section: Resultsmentioning

confidence: 99%

Dysregulation of global circular RNA abundance regulated by spliceosomes predicts prognosis in hepatocellular carcinoma

Qiu

Chen

et al. 2022

Hepatol Commun

View full text Add to dashboard Cite

show abstract

“…Previously, we reported that FAM122A inhibits the phosphatase activity of protein phosphatases of the type 2A family (PP2A) by interacting with its Aa scaffold and Ba regulatory subunits (Fan et al, 2016), a major fraction of cellular Ser/Thr phosphatase activity in any given human tissue, to play important roles in germ cell maturation, embryonic development, metabolic regulation, tumor suppression, and homeostasis of many adult organs (Reynhout and Jans-sens, 2019). We also demonstrated that FAM122A is critical for maintaining the growth of hepatocellular carcinoma cells and acute myeloid leukemia (AML) cells in a PP2A activity-independent or -dependent manner (Liu et al, 2020;Zhou et al, 2020). However, the biological functions of FAM122A protein are poorly understood to date.…”

Section: Introductionmentioning

confidence: 97%

FAM122A Inhibits Erythroid Differentiation through GATA1

et al. 2020

Self Cite

View full text Add to dashboard Cite

Summary FAM1 22A is a highly conserved housekeeping gene, but its physiological and pathophysiological roles remain greatly elusive. Based on the fact that FAM1 22A is highly expressed in human CD71 + early erythroid cells, herein we report that FAM122A is downregulated during erythroid differentiation, while its overexpression significantly inhibits erythrocytic differentiation in primary human hematopoietic progenitor cells and erythroleukemia cells. Mechanistically, FAM122A directly interacts with the C-terminal zinc finger domain of GATA1, a critical transcriptional factor for erythropoiesis, and reduces GATA1 chromatin occupancy on the promoters of its target genes, thus resulting in the decrease of GATA1 transcriptional activity. The public datasets show that FAM1 22A is abnormally upregulated in patients with β-thalassemia. Collectively, our results demonstrate that FAM122A plays an inhibitory role in the regulation of erythroid differentiation, and it would be a potentially therapeutic target for GATA1-related dyserythropoiesis or an important regulator for amplifying erythroid cells ex vivo .

show abstract

“…It was shown that FAM122A (family with sequence similarity 122a), a highly conserved protein among a variety of mammalian species, interacts with PP2A-Aα and -B55α (a scaffold and regulatory subunit of PP2A complex) and promotes the polyubiquitination and degradation of its Cα subunit (7), and FAM122A sumoylation increases the degradation of PP2A-Cα protein together with the reduced phosphatase activity of PP2A (8). Recently, we demonstrate that FAM122A maintains the growth of hepatocellular carcinoma cells through promoting MAPK/AKT signaling (9). However, the normal function and pathophysiological significance of FAM122A are still largely unknown so far.…”

mentioning

confidence: 92%

FAM122A promotes acute myeloid leukemia cell growth through inhibiting PP2A activity and sustaining MYC expression

et al. 2020

View full text Add to dashboard Cite

show abstract

FAM122A supports the growth of hepatocellular carcinoma cells and its deletion enhances Doxorubicin-induced cytotoxicity

Cited by 13 publications

References 37 publications

Dysregulation of global circular RNA abundance regulated by spliceosomes predicts prognosis in hepatocellular carcinoma

Dysregulation of global circular RNA abundance regulated by spliceosomes predicts prognosis in hepatocellular carcinoma

FAM122A Inhibits Erythroid Differentiation through GATA1

FAM122A promotes acute myeloid leukemia cell growth through inhibiting PP2A activity and sustaining MYC expression

Contact Info

Product

Resources

About