Deficiency of pseudogene UPAT leads to hepatocellular carcinoma progression and forms a positive feedback loop with ZEB1

Xiang, Leyang; Huang, Xiaoting; Wang, Siqi; Ou, Huohui; Chen, Zhanjun; Hu, Zhigang; Huang, Yu; Li, Xianghong; Yuan, Yawei; Yang, Dian

doi:10.1111/cas.14620

Cited by 7 publications

(9 citation statements)

References 39 publications

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“…WFDC21P is lower expressed in carcinoma tissues than in paired paracarcinoma tissues, and its expression levels are decreased as HCC progresses [72]. AOC4P (UPAT) is downregulated in 39.78% of individuals with HBV-related HCC [73]. GOLGA2P10 is upregulated in HCC tissues and cells treated with ER stress inducers (tunicamycin and thapsigargin) [74].…”

Section: Cancers Located In the Abdomen And Bonesmentioning

confidence: 99%

The World of Pseudogenes: New Diagnostic and Therapeutic Targets in Cancers or Still Mystery Molecules?

Stasiak

Kolenda

Kozłowska-Masłoń

et al. 2021

Life

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Pseudogenes were once considered as “junk DNA”, due to loss of their functions as a result of the accumulation of mutations, such as frameshift and presence of premature stop-codons and relocation of genes to inactive heterochromatin regions of the genome. Pseudogenes are divided into two large groups, processed and unprocessed, according to their primary structure and origin. Only 10% of all pseudogenes are transcribed into RNAs and participate in the regulation of parental gene expression at both transcriptional and translational levels through senseRNA (sRNA) and antisense RNA (asRNA). In this review, about 150 pseudogenes in the different types of cancers were analyzed. Part of these pseudogenes seem to be useful in molecular diagnostics and can be detected in various types of biological material including tissue as well as biological fluids (liquid biopsy) using different detection methods. The number of pseudogenes, as well as their function in the human genome, is still unknown. However, thanks to the development of various technologies and bioinformatic tools, it was revealed so far that pseudogenes are involved in the development and progression of certain diseases, especially in cancer.

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Section: Cancers Located In the Abdomen And Bonesmentioning

confidence: 99%

The World of Pseudogenes: New Diagnostic and Therapeutic Targets in Cancers or Still Mystery Molecules?

Stasiak

Kolenda

Kozłowska-Masłoń

et al. 2021

Life

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“…39,40 AOC4P had been studied primarily only in tumors. 41 In this study, we first examined the expression of AOC4P in PCOS GCs and this downregulation was subsequently confirmed. Then, we hypothesized that AOC4P might mediate the Our study firstly confirmed the low expression of AOC4P in GCs of PCOS patients.…”

Section: Discussionmentioning

confidence: 85%

“…Some studies had established characteristic lncRNA expression profiles, attempting to use it as diagnostic or prognostic markers for different diseases 39,40 . AOC4P had been studied primarily only in tumors 41 . In this study, we first examined the expression of AOC4P in PCOS GCs and this downregulation was subsequently confirmed.…”

Section: Discussionmentioning

confidence: 92%

LncRNA AOC4P impacts the differentiation of macrophages and T‐lymphocyte by regulating the NF‐κB pathways of KGN cells: Potential pathogenesis of polycystic ovary syndrome

Yang,

Wu,

et al. 2023

American J Rep Immunol

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BackgroundPolycystic ovary syndrome (PCOS) is a multifactorial endocrine disease, which is an important cause of female infertility worldwide. PCOS patients are in a state of chronic low‐grade inflammation, and immune imbalance is considered as a potential cause of its pathogenesis.MethodsThe expression of AOC4P in PCOS and normal ovarian granulosa cells (GCs) was detected by real‐time quantitative PCR. KGN cells were induced by dihydrotestosterone at 500 ng/mL to construct the PCOS model. After lentivirus‐infected, KGN cells were constructed with AOC4P overexpression cell lines, the proliferation and apoptosis levels of KGN cells in AOC4P and NC groups were detected. Human monocyte cell line (THP‐1)‐derived macrophages and peripheral blood mononuclear cells (PBMC) were co‐cultured with KGN cells for 48 h, respectively, and the differentiation of macrophages and CD4+ T cells were detected by flow cytometry.ResultsDecreased AOC4P expression was found in PCOS patients. After constructing the PCOS cell model, we observed that overexpression of AOC4P promoted KGN cell proliferation and inhibited apoptosis. After co‐culture with AOC4P overexpressed KGN cells, M1 macrophages decreased, M2 macrophages increased, T helper cells type 1 (Th1)/Th2 ratio increased, and regulatory T cell (Treg) cells increased. Finally, we found that AOC4P inhibited the activation of the nuclear factor κ B (NF‐κB) pathway in KGN cells.ConclusionsIn this study, we found that AOC4P regulated the NF‐κB signaling pathway by inhibiting the phosphorylation of P65, thereby affecting the proliferation and apoptosis of GCs, altering the differentiation of macrophages and T cells, thus contributing to the pathogenesis of PCOS.

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“…Earlier studies have exhibited abnormal expression of pseudogenes in a variety of tumors, such as colorectal cancer, HCC, renal cell carcinoma, and gastric cancer (Chen et (Hu et al 2020). In our work, we found that the pseudogene CTB-63M22.1 has the same mutation frequency and co-expression module as mRNAsi.…”

Section: Discussionmentioning

confidence: 99%

Identification of potential pseudogenes for predicting the prognosis of hepatocellular carcinoma

Jin

Zhang

et al. 2023

Preprint

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Purpose Hepatocellular carcinoma (HCC) remains a highly deadly malignant tumor with high recurrence and metastasis rates. Cancer stem cells (CSCs) are involved in tumor metastasis, recurrence, and resistance to drugs, which have attracted widespread attention in recent years. Research has shown that pseudogenes may regulate stemness to promote the progression of HCC, but its specific mechanisms and impact on prognosis remain unclear. Methods In this study, clinical prognosis information of HCC was first downloaded from The Cancer Genome Atlas (TCGA) database. Then we calculated the mRNA expression based stemness index (mRNAsi) of HCC. We also screened the differentially expressed Pseudogene (DEPs) and conducted univariate Cox regression analysis to investigate their effect on the prognosis of HCC. Further, genomic mutation frequency analysis and weighted gene co-expression network analysis (WGCNA) were performed to compare the role of pseudogenes and stemness in promoting the progression of HCC. Finally, we conducted the correlation analysis to examine the potential mechanism of pseudogenes regulating stemness to promote the progression of HCC and detected the possible pathways through the Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results Herein, we revealed that the high stemness of HCC correlated with an unfavorable prognosis. We obtained 31 up-regulated and 8 down-regulated DEPs in HCC and screened CTB-63M22.1, a poor prognostic indicator of HCC. In addition, CTB-63M22.1 had a mutation frequency similar to mRNAsi and acted in a module similar to that of mRNAsi on HCC. We then screened two RNA-binding proteins (RBPs) LIN28B and NOP56 with the highest correlation with stemness. We also discovered that they were primarily enriched in the biological process as examples of mitotic nuclear division and cell cycle. Conclusions Collectively, these results revealed that pseudogenes CTB-63M22.1 may regulate cancer stemness by regulating RBPs, suggesting that CTB-63M22.1 may serve as an innovative therapeutic target and a reliable prognostic marker for HCC.

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Deficiency of pseudogene UPAT leads to hepatocellular carcinoma progression and forms a positive feedback loop with ZEB1

Cited by 7 publications

References 39 publications

The World of Pseudogenes: New Diagnostic and Therapeutic Targets in Cancers or Still Mystery Molecules?

The World of Pseudogenes: New Diagnostic and Therapeutic Targets in Cancers or Still Mystery Molecules?

LncRNA AOC4P impacts the differentiation of macrophages and T‐lymphocyte by regulating the NF‐κB pathways of KGN cells: Potential pathogenesis of polycystic ovary syndrome

Identification of potential pseudogenes for predicting the prognosis of hepatocellular carcinoma

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