The basal transcription machinery as a target for cancer therapy

Villicaña, Claudia; Cruz, Grisel; Zurita, Mario

doi:10.1186/1475-2867-14-18

Cited by 59 publications

(44 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed a vast majority of our identified circRNA candidates (86%) containing a transposable element sequence (SINE/LINE) in the flanks of backsplice forming exons (Supplementary Figure S4) that could in-part explain the presence of many low frequency circular isoforms from multi-exon genes. In addition, enhanced transcription of oncogenes and other transcription factors in cancer cells [55, 56] could lead to inefficient canonical splicing due to an accelerated polymerase activity. This may also give rise to many of the low abundance circular structures as biogenesis of circRNAs has been shown to be negatively correlated with splicing efficiency [18].…”

Section: Discussionmentioning

confidence: 99%

Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma

et al. 2016

View full text Add to dashboard Cite

Recently, a class of endogenous species of RNA called circular RNA (circRNA) has been shown to regulate gene expression in mammals and their role in cellular function is just beginning to be understood. To investigate the role of circRNAs in ovarian cancer, we performed paired-end RNA sequencing of primary sites, peritoneal and lymph node metastases from three patients with stage IIIC ovarian cancer. We developed an in-house computational pipeline to identify and characterize the circRNA expression from paired-end RNA-Seq libraries. This pipeline revealed thousands of circular isoforms in Epithelial Ovarian Carcinoma (EOC). These circRNAs are enriched for potentially effective miRNA seed matches. A significantly larger number of circRNAs are differentially expressed between tumor sites than mRNAs. Circular and linear expression exhibits an inverse trend for many cancer related pathways and signaling pathways like NFkB, PI3k/AKT and TGF-β typically activated for mRNA in metastases are inhibited for circRNA expression. Further, circRNAs show a more robust expression pattern across patients than mRNA forms indicating their suitability as biomarkers in highly heterogeneous cancer transcriptomes. The consistency of circular RNA expression may offer new candidates for cancer treatment and prognosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma

et al. 2016

View full text Add to dashboard Cite

show abstract

“…BRD4 was found overexpressed in different tumor types such as acute myeloid or lymphoid leukemia (AML and ALL), malignant melanoma, and lung adenocarcinoma . Furthermore, it has been shown that transcriptional inhibition has a direct cytotoxic effect on malignant cells and thus, the basal transcription machinery is a promising druggable target to block cancer cell proliferation . From this perspective, BRD4 inhibition is an emerging relevant strategy for the treatment of various cancers.…”

Section: Discussionmentioning

confidence: 99%

“…47 Furthermore, it has been shown that transcriptional inhibition has a direct cytotoxic effect on malignant cells and thus, the basal transcription machinery is a promising druggable target to block cancer cell proliferation. 48 From this perspective, BRD4 inhibition is an emerging relevant strategy for the treatment of various cancers. JQ1, a BRD4 inhibitor, is a thieno-triazolo-1,4-diazepine that displaces BET bromodomains from chromatin through recognition pocket, preventing BRD4 reading activity.…”

Section: Discussionmentioning

confidence: 99%

Histo‐genomic stratification reveals the frequent amplification/overexpression of CCNE1 and BRD4 genes in non‐BRCAness high grade ovarian carcinoma

Goundiam

Gestraud

Popova

et al. 2015

Intl Journal of Cancer

View full text Add to dashboard Cite

The treatment of epithelial ovarian cancer (EOC) is narrowly focused despite the heterogeneity of this disease in which outcomes remain poor. To stratify EOC patients for targeted therapy, we developed an approach integrating expression and genomic analyses including the BRCAness status. Gene expression and genomic profiling were used to identify genes recurrently (>5%) amplified and overexpressed in 105 EOC. The LST (Large-scale State Transition) genomic signature of BRCAness was applied to define molecular subgroups of EOC. Amplified/overexpressed genes clustered mainly in 3q, 8q, 19p and 19q. These changes were generally found mutually exclusive. In the 85 patients for which the genomic signature could be determined, genomic BRCAness was found in 52 cases (61.1%) and non-BRCAness in 33 (38.8%). A striking mutual exclusivity was observed between BRCAness and amplification/overexpression data. Whereas 3q and 8q alterations were preferentially observed in BRCAness EOC, most alterations on chromosome 19 were in non-BRCAness cases. CCNE1 (19q12) and BRD4 (19p13.1) amplification/overexpression was found in 19/33 (57.5%) of non-BRCAness cases. Such disequilibrium was also found in the TCGA EOC data set used for validation. Potential target genes are frequently amplified/overexpressed in non-BRCAness EOC. We report that BRD4, already identified as a target in several tumor models, is a new potential target in high grade non-BRCAness ovarian carcinoma.Epithelial ovarian cancer (EOC) is the seventh most common cause of cancer related death in women. 1 This high mortality rate is a result of delayed diagnosis and limited therapeutic options. The reference treatment of EOC is an association of surgical cytoreduction and platinum-based chemotherapy. About 80% of tumors respond to the first line of treatment 2 but a relapse develops in most cases and there is no curative treatment for recurrent diseases.EOC spans many diseases that differ in their histology, primary anatomical location and molecular features. Histologically, serous (40%), endometrioid (24%) mucinous (6%) and clear cells (26%) are the most frequent. 3 The classical three-tier histological grading system was recently modified as a binary system for serous carcinoma. 4 Anatomically, though a subset of endometrioid and clear cell carcinoma are known to develop from pelvic endometriosis, the extensive study of prophylactic oophoro-salpingectomy specimens revealed that a notable proportion of high grade serous ovarian cancers are actually derived from the distal fallopian tube. 5 Bio-pathological studies have shown that histological subtypes progress through distinct biological pathways. Two

show abstract

“…It is well established that cancer cells require high levels of transcription to survive and to maintain their malignant phenotype 40. Therefore, the components of the basal transcription machinery could be considered good targets to reduce global transcription, and they might have stronger effects in cancer cells when compared with non-cancerous cells (reviewed in 39).…”

Section: Tfiih As a Target For Cancer Therapymentioning

confidence: 99%

TFIIH: New Discoveries Regarding its Mechanisms and Impact on Cancer Treatment

Zurita¹,

Cruz‐Becerra²

2016

J. Cancer

Self Cite

View full text Add to dashboard Cite

The deregulation of gene expression is a characteristic of cancer cells, and malignant cells require very high levels of transcription to maintain their cancerous phenotype and survive. Therefore, components of the basal transcription machinery may be considered as targets to preferentially kill cancerous cells. TFIIH is a multisubunit basal transcription factor that also functions in nucleotide excision repair. The recent discoveries of some small molecules that interfere with TFIIH and that preferentially kill cancer cells have increased researchers' interest to elucidate the complex mechanisms by which TFIIH operates. In this review, we summarize the knowledge generated during the 25 years of TFIIH research, highlighting the recent advances in TFIIH structural and mechanistic analyses that suggest the potential of TFIIH as a target for cancer treatment.

show abstract

The basal transcription machinery as a target for cancer therapy

Cited by 59 publications

References 107 publications

Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma

Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma

Histo‐genomic stratification reveals the frequent amplification/overexpression of CCNE1 and BRD4 genes in non‐BRCAness high grade ovarian carcinoma

TFIIH: New Discoveries Regarding its Mechanisms and Impact on Cancer Treatment

Contact Info

Product

Resources

About