Expression of TRA2B in endometrial carcinoma and its regulatory roles in endometrial carcinoma cells

Paudel, Dhruba; Ouyang, Yan‐Qiong; Huang, Qingting; Zhou, Weiping; Wang, Jianjun; Poorekhorsandi, Maxwell Enayat; Dhakal, Bipin; Tong, Xiaowen

doi:10.3892/ol.2019.10553

Cited by 5 publications

(3 citation statements)

References 46 publications

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“…Several studies have revealed that TRA2B can inhibit cellular apoptosis or promote invasion in several cancers [ 19 , 20 ]. Both the TRA2B messenger RNA (mRNA) and Tra2β protein levels are increased in many cancers [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Transformer 2β regulates the alternative splicing of cell cycle regulatory genes to promote the malignant phenotype of ovarian cancer

Zhou¹,

Fu²,

Chen³

et al. 2023

Oncology Research

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Late-stage ovarian cancer (OC) has a poor prognosis and a high metastasis rate, but the underlying molecular mechanism is unclear. RNA binding proteins (RBPs) play important roles in posttranscriptional regulation in the contexts of neoplasia and tumor metastasis. In this study, we explored the molecular functions of a canonical RBP, Transformer 2β homolog (TRA2B), in cancer cells. TRA2B knockdown in HeLa cells and subsequent whole-transcriptome RNA sequencing (RNA-seq) analysis revealed the TRA2B-regulated alternative splicing (AS) profile. We disrupted TRA2B expression in epithelial OC cells and performed a series of experiments to confirm the resulting effects on OC cell proliferation, apoptosis and invasion. TRA2B-regulated AS was tightly associated with the mitotic cell cycle, apoptosis and several cancer pathways. Moreover, the expression of hundreds of genes was regulated by TRA2B, and these genes were enriched in the functions of cell proliferation, cell adhesion and angiogenesis, which are related to the malignant phenotype of OC. By integrating the alternatively spliced and differentially expressed genes, we found that AS events and gene expression were regulated independently. We then explored and validated the oncogenic functions of TRA2B by knocking down its expression in OC cells. The high TRA2B expression was associated with poor prognosis in patients with OC. In ovarian tissue, TRA2B expression showed a gradual increasing trend with increasing malignancy. We demonstrated the important roles of TRA2B in ovarian neoplasia and aggressive OC behaviors and identified the underlying molecular mechanisms, facilitating the targeted treatment of OC.

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Section: Introductionmentioning

confidence: 99%

Transformer 2β regulates the alternative splicing of cell cycle regulatory genes to promote the malignant phenotype of ovarian cancer

Zhou¹,

Fu²,

Chen³

et al. 2023

Oncology Research

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show abstract

“…Transformer 2β (Tra2β) contains two serine/arginine domains and an RNA recognition motif, and it functions as a sequence-specific pre-mRNA splicing enhancer 9 , 10 . Overexpression of the Tra2β protein is associated with the development of several cancers 11 – 14 . We previously reported that the protein and mRNA levels of Tra2β were upregulated in colon cancer cells, and silencing of Tra2β decreased colon cancer cell proliferation 15 .…”

Section: Introductionmentioning

confidence: 99%

Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression

Kuwano

Nishida

Rokutan

2021

Sci Rep

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Ultraconserved regions (UCRs) are 481 genomic sequences with 100% identity across humans, rats, and mice. Increasing evidence suggests that non-coding RNAs transcribed from UCRs are involved in various diseases, especially cancers. The human transformer 2β gene (TRA2B) encodes a UCR (uc.138) that spans exon 2 and its neighboring introns. TRA2B4 RNA is the only transcript that contains the whole exon 2 among five spliced TRA2B RNA variants (TRA2B1-5). TRA2B4 is upregulated in colon cancer cell lines, although it is not translated to Tra2β protein because of its nuclear retention. Nevertheless, the clinical significance and biological functions of uc.138 in colon cancer cells remain unclear. In this study, RNA in situ hybridization showed that TRA2B4 was predominantly overexpressed in the nucleus of colon adenocarcinoma and adenoma. Overexpression of TRA2B4 in colon cancer HCT116 cells promoted cell proliferation by changing the expression of G2/M-related cell cycle regulators. Moreover, TRA2B4 increased migration and cell viability in a uc.138 sequence-dependent manner. TRA2B4 significantly enhanced tumorigenesis in vivo. Taken together, uc.138 encoded in TRA2B4 plays an oncogenic role in tumor progression and may become a potential biomarker and therapeutic target in colon cancer.

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“…A recent study confirmed the regulatory role of TRA2B in EC with overexpression of TRA2B clearly correlating with increased proliferation of EC cells. In addition, inhibition of TRA2B expression by siRNA reversed these effects and increased apoptosis ( 17 ), suggesting not only prognostic role of TRA2B expression, but also making this gene a potential target for development of EC treatment. Another possibility is the presence of SOX17.…”

Section: Introductionmentioning

confidence: 99%

Endometrial cancer—is our knowledge changing?

Králíčková¹,

Větvička²,

Laganà³

2020

Transl Cancer Res TCR

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In developed countries, endometrial cancer (EC) is the most frequent gynecologic malignancy in postmenopausal women. At the same time, EC has become one of the most common cancers in numerous developing countries, probably influenced by global epidemic of obesity. The majority of patients have lowgrade endometrioid cancer with a high 5-year survival rate, but with high-risk EC, the survival rates are still rather low. However, despite intensive research in last decades, our knowledge of the mechanisms, risk factors, diagnosis and treatment have not significantly improved. The standard treatment of all types of EC is still a traditional combination of surgery, irradiation and/or chemotherapy, despite the fact that each of these options is not without having some negative side effects. Despite the fact that on the molecular level, EC is relatively well-studied, but the efforts to transform these findings into either diagnosis or therapies of EC remain elusive. In addition, some research into risk factors involved in the development or progression of EC seems to be more a fishing expedition than a well thought-out approach. The purpose of this review is to summarize the most recent developments in the search for biomarkers and prognostic markers and to discuss the progress in EC treatment.

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Expression of TRA2B in endometrial carcinoma and its regulatory roles in endometrial carcinoma cells

Cited by 5 publications

References 46 publications

Transformer 2β regulates the alternative splicing of cell cycle regulatory genes to promote the malignant phenotype of ovarian cancer

Transformer 2β regulates the alternative splicing of cell cycle regulatory genes to promote the malignant phenotype of ovarian cancer

Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression

Endometrial cancer—is our knowledge changing?

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