The EZH2–PHACTR2–AS1–Ribosome Axis induces Genomic Instability and Promotes Growth and Metastasis in Breast Cancer

Chu, Wenhui; Zhang, Xi; Liu, Qi; Fu, Yenan; Wang, Peng; Zhao, Wei; Du, Juan; Zhang, Jing; Zhan, Jun; Wang, Yunling; Zhu, Weiguo; Yu, Yu; Zhang, Hongquan

doi:10.1158/0008-5472.can-19-3326

Cited by 53 publications

(33 citation statements)

References 44 publications

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“…In prostate cancer, it was reported that the elevated expression of SUV39H1 promotes cancer cell aggression [31] . In breast cancer, SUV39H1 binds to PHACTR2-AS1-30nt-RNA, silences DNA genes and then restrains breast cancer progression and lung metastasis in mice [32] . In malignant brain glioma, tumors can be suppressed by repressive targets of SUV39H1 [33] .…”

Section: Discussionmentioning

confidence: 99%

Clinical expression and prognosis of SUV39H1 in diffuse large B-cell lymphoma

Zhang¹,

Wen²,

Lei³

et al. 2021

Preprint

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Background: Epigenetic regulation plays vital roles in the oncogenesis and treatment of diffuse large B-cell lymphoma (DLBCL). The H3K9me3-specific histone methyltransferase SUV39H1 is an epigenetic gene that promotes the progression of a variety of malignancies. However, the roles of SUV39H1 in DLBCL remain unclear.Methods: Initially, the Oncomine, Cancer Cell Line Encyclopedia (CCLE), UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) databases were searched to explore the expression of SUV39H1 in DLBCL. The clinical parameters and pathological sections of 61 successive patients, including 47 cases of DLBCL and 14 cases of reactive lymphoid hyperplasia, were collected from January 2019 to November 2020. Immunohistochemistry was conducted to verify the results of the database search. Finally, relevant parameters and pathological results were combined to analyze the expression of SUV39H1.Results: We found that the expression of SUV39H1 in DLBCL tissues was higher than that in normal and other cancer tissues (P<0.05) in database and immunohistochemistry analyses. Among the analyzed clinical parameters, only tumor size was closely associated with SUV39H1 (P=0.037), suggesting that patients with high SUV39H1 expression are less likely to develop tumors over 7.5 cm in size. Regarding survival, the group with high SUV39H1 expression had a lower survival rate than the group with low SUV39H1 expression in terms of 10-year disease-free survival (DFS) according to the database analyses (P=0.035). However, SUV39H1 was revealed as an independent predictor of overall survival (OS) and progression-free survival (PFS) in patients from both databases and our hospital (P>0.05).Conclusion: SUV39H1 expression is higher in DLBCL tissues than in normal and other cancer tissues, indicating that DLBCL patients may not develop bulky tumors over follow-up and suggesting that SUV39H1 might serve not only as a predictive factor in the clinic but also as a target for the epigenetic therapy of DLBCL.

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Section: Discussionmentioning

confidence: 99%

Clinical expression and prognosis of SUV39H1 in diffuse large B-cell lymphoma

Zhang¹,

Wen²,

Lei³

et al. 2021

Preprint

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“…Recent studies showed the effects of FTO 77 , protein arginine methyltransferase 1 (PRMT1) 78 , coactivator associated arginine methyltransferase 1 (CARM1)/PRMT4 79 , Otubain-2 (OTUB2) 80 , RING finger protein 144A (RNF144A) 81 , plant homeodomain finger protein 20-like protein 1 (PHF20L1) 82 , heat shock transcription factor 1 (HSF1) 83 , epithelial cell transforming sequence 2 (ECT2) 84 , pescadillo homolog 1 (PES1) 85 , PHACTR2-AS1 (PAS1) 86 , breast cancer-related transcript 1 (BCRT1) 87 , and circCDYL 88 on progression of breast cancer and they provided novel therapeutic targets. TNBC is especially hard to treat due to the lack of targets.…”

Section: Novel Therapeutic Targets and New Drugsmentioning

confidence: 99%

Progress of Breast Cancer basic research in China

Wang

Guan

et al. 2021

Int. J. Biol. Sci.

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Breast cancer is the most commonly diagnosed and the most lethal cancer in females both in China and worldwide. Currently, the origin of cancer stem cells, the heterogeneity of cancer cells, the mechanism of cancer metastasis and drug resistance are the most important issues that need to be addressed. Chinese investigators have recently made new discoveries in basic breast cancer researches, especially regarding cancer stem cells, cancer metabolism, and microenvironments. These efforts have led to a deeper understanding of drug resistance and metastasis and have also indicated new biomarkers and therapeutic targets. These findings emphasized the importance of the cancer stem cells for targeted therapy. In this review, we summarized the latest important findings in this field in China.

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“…It is differentially expressed in lung adenocarcinoma (47), and polymorphisms in the gene have been shown to affect DNA repair capacity, which is a risk factor for lung cancer (48). Long noncoding antisense RNA PHACTR2-AS1 has been shown to promote metastasis in breast cancer (49). Good potential causal variants were identified at rs966382235, rs79313503, and rs553447284.…”

Section: Candidate Genes -Utrn and Phactr2mentioning

confidence: 99%

Genetic Variation and Recurrent Haplotypes on Chromosome 6q23-25 Risk Locus in Familial Lung Cancer

et al. 2021

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While lung cancer is known to be caused by environmental factors, it has also been shown to have genetic components, and the genetic etiology of lung cancer remains understudied. We previously identified a lung cancer risk locus on 6q23-25 using microsatellite data in families with a history of lung cancer. To further elucidate that signal, we performed targeted sequencing on 9 of our most strongly linked families. Two-point linkage analysis of the sequencing data revealed that the signal was heterogeneous and that different families likely had different risk variants. Three specific haplotypes were shared by some of the families: 6q25.3-26 in families 42 and 44, 6q25.2-25.3 in families 47 and 59, and 6q24.2-25.1 in families 30, 33, and 35. Region-based LOD scores and expression data identified the likely candidate genes for each haplotype overlap: ARID1B at 6q25.3, MAP3K4 at 6q26, and UTRN (6q24.1) and PHACTR2 (6q24.2). Further annotation was used to zero in on potential risk variants in those genes. All four genes are good candidate genes for lung cancer risk, having been linked to either lung cancer specifically or other cancers. However, this is the first time any of these genes has been implicated in germline risk. Functional analysis of these four genes is planned for future work.

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The EZH2–PHACTR2–AS1–Ribosome Axis induces Genomic Instability and Promotes Growth and Metastasis in Breast Cancer

Cited by 53 publications

References 44 publications

Clinical expression and prognosis of SUV39H1 in diffuse large B-cell lymphoma

Clinical expression and prognosis of SUV39H1 in diffuse large B-cell lymphoma

Progress of Breast Cancer basic research in China

Genetic Variation and Recurrent Haplotypes on Chromosome 6q23-25 Risk Locus in Familial Lung Cancer

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