A hypermethylation strategy utilized by enhancer-bound CARM1 to promote estrogen receptor α-dependent transcriptional activation and breast carcinogenesis

Peng, Bing‐ling; Li, Wenjuan; Ding, Jian; He, Yaohui; Ran, Ting; Xie, Bing-Lan; Wang, Zi-Rui; Shen, Hai‐feng; Xiao, Rong-quan; Gao, Weiwei; Ye, Tian-yi; Gao, Xiang; Li, Wen

doi:10.7150/thno.39241

Cited by 37 publications

(40 citation statements)

References 64 publications

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“…The would-healing assay was performed as described [ 34 ]. For each cell type, an equal number of cells was plated in triplicate in 6-well dishes and inoculated to ensure that the fusion degree of the cells after attachment was 90%.…”

Section: Methodsmentioning

confidence: 99%

“…Transwell assays were performed as described [ 34 ]. Using 24-well plates, 700 μl of medium containing 20% FBS was added to each well, and Transwell chambers with an 8 μm pore size were gently inserted into each well.…”

Section: Methodsmentioning

confidence: 99%

“…All animals were maintained in pathogen-free conditions and in accordance with the guidelines of the Institutional Animal Care and Use Committee. Six weeks after injection with T47D cells and 3 weeks after injection with MDA-MB-231 cells, mice were euthanized, and tumors were extracted for further analysis [ 34 ]. The tumor volume was calculated using the following formula: tumor volume = length*width 2 /2 [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

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Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1

Luo

Zhang

et al. 2021

J Exp Clin Cancer Res

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Background Intensive evidence has highlighted the effect of aberrant alternative splicing (AS) events on cancer progression when triggered by dysregulation of the SR protein family. Nonetheless, the underlying mechanism in breast cancer (BRCA) remains elusive. Here we sought to explore the molecular function of SRSF1 and identify the key AS events regulated by SRSF1 in BRCA. Methods We conducted a comprehensive analysis of the expression and clinical correlation of SRSF1 in BRCA based on the TCGA dataset, Metabric database and clinical tissue samples. Functional analysis of SRSF1 in BRCA was conducted in vitro and in vivo. SRSF1-mediated AS events and their binding motifs were identified by RNA-seq, RNA immunoprecipitation-PCR (RIP-PCR) and in vivo crosslinking followed by immunoprecipitation (CLIP), which was further validated by the minigene reporter assay. PTPMT1 exon 3 (E3) AS was identified to partially mediate the oncogenic role of SRSF1 by the P-AKT/C-MYC axis. Finally, the expression and clinical significance of these AS events were validated in clinical samples and using the TCGA database. Results SRSF1 expression was consistently upregulated in BRCA samples, positively associated with tumor grade and the Ki-67 index, and correlated with poor prognosis in a hormone receptor-positive (HR+) cohort, which facilitated proliferation, cell migration and inhibited apoptosis in vitro and in vivo. We identified SRSF1-mediated AS events and discovered the SRSF1 binding motif in the regulation of splice switching of PTPMT1. Furthermore, PTPMT1 splice switching was regulated by SRSF1 by binding directly to its motif in E3 which partially mediated the oncogenic role of SRSF1 by the AKT/C-MYC axis. Additionally, PTPMT1 splice switching was validated in tissue samples of BRCA patients and using the TCGA database. The high-risk group, identified by AS of PTPMT1 and expression of SRSF1, possessed poorer prognosis in the stage I/II TCGA BRCA cohort. Conclusions SRSF1 exerts oncogenic roles in BRCA partially by regulating the AS of PTPMT1, which could be a therapeutic target candidate in BRCA and a prognostic factor in HR+ BRCA patient.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1

Luo

Zhang

et al. 2021

J Exp Clin Cancer Res

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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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“…Peptides were recovered by transfer-ring the filter to a new collection tube and spinning at 14,000 g. To increase the yield of peptides, the filter was washed twice with 100 mL of 50 mM ammonium bicarbonate. Peptides were desalted by StageTips (34,35). GO and KEGG pathway analysis Gene Ontology (GO) is an ontology widely used in the field of bioinformatics for annotating large scale genes and gene products (36).…”

Section: Lc-ms Analysis and Database Searchmentioning

confidence: 99%

SNAPIN Regulates Cell Cycle Progression to Promote Pancreatic β Cell Growth

Jiang

Kuang

et al. 2021

Front. Endocrinol.

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In diabetes mellitus, death of β cell in the pancreas occurs throughout the development of the disease, with loss of insulin production. The maintenance of β cell number is essential to maintaining normoglycemia. SNAPIN has been found to regulate insulin secretion, but whether it induces β cell proliferation remains to be elucidated. This study aimed to explore the physiological roles of SNAPIN in β cell proliferation. SNAPIN expression increases with the age of mice and SNAPIN is down-regulated in diabetes. KEGG pathway and GO analysis showed that SNAPIN- interacting proteins were enriched in cell cycle regulation. B cell cycle was arrested in the S phase, and cell proliferation was inhibited after SNAPIN knockdown. The expression of CDK2, CDK4 and CCND1 proteins in the S phase of the cell cycle were reduced after SNAPIN knockdown, whereas they were increased after overexpression of SNAPIN. In addition, insulin protein and mRNA levels also increased or decreased after SNAPIN knockdown or overexpression, respectively. Conclusions: Our data indicate that SNAPIN mediates β cells proliferation and insulin secretion, and provide evidences that SNAPIN might be a pharmacotherapeutic target for diabetes mellitus.

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A hypermethylation strategy utilized by enhancer-bound CARM1 to promote estrogen receptor α-dependent transcriptional activation and breast carcinogenesis

Cited by 37 publications

References 64 publications

Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1

Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1

Progress of Breast Cancer basic research in China

SNAPIN Regulates Cell Cycle Progression to Promote Pancreatic β Cell Growth

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