NFYB-induced high expression of E2F1 contributes to oxaliplatin resistance in colorectal cancer via the enhancement of CHK1 signaling

Fang, Zejun; Gong, Chaoju; Yu, Songshan; Zhou, Weihua; Hassan, Waseem; Li, Hongzhang; Wang, Xue; Hu, Yifei; Gu, Kaipeng; Chen, Xixi; Hu, Bing; Bao, Yu; Chen, Xiang; Zhang, Xiaomin; Liu, Hong

doi:10.1016/j.canlet.2017.11.040

Cited by 56 publications

(36 citation statements)

References 38 publications

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“…A research reported suppressive function of E2F1 showed that the absence of E2F1 gene lead to an increased incidence and progression of tumorigenesis induced by PTEN loss [23]. While others found that E2F1 was overexpressed in CRC patients [25] and E2F1 could promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2 [12]. In this study, we disclosed that the mRNA expression of E2F1 was signi cantly higher in both COAD and READ based on ONCOMINE and TCGA datasets.…”

Section: Discussionmentioning

confidence: 59%

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A Research of the Predictive Values of E2F Factors in Colorectal Cancer

Zhang¹,

Yang²,

Zhang³

et al. 2020

Preprint

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Background: E2F family of transcription factors are related to cell cycle and apoptosis with activate or repress function on human cancer. Their critical role in colorectal cancer (CRC), including colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), were widely investigated with contradictory and ambiguous results. Methods: In this study, we explored the expressions of these eight E2F genes and their predictive values on the overall survive (OS) and disease-free survival (DFS) in CRC patients by means of bioinformatic databases, such as ONCOMINE, GEPIA, DAVIA and cBioPortal.Results: We found that the transcriptional levels of E2F1/2/3/5/7/8 were significantly higher in CRC patients than that in normal samples, while the E2F4/6 showed no significantly difference from GEPIA database. The transcriptional levels of all eight E2F factors showed no correlation with four tumor stages, except for the E2F3 is significantly varied in COAD patients. Survival analysis based on GEPIA database indicated that lower E2F3 and E2F4 mRNA expressions were significantly associated with the OS of the COAD patients.Conclusions: This study manifested that the E2F1/2/3/5/7/8 are potential biomarkers of CRC patients, and E2F3 could be used as the predictive factor of tumor stage in COAD patients. E2F3 and E2F4 might be the prognostic markers for COAD patients.

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Section: Discussionmentioning

confidence: 59%

“…Among all these E2F family, E2F1 is the most extensively investigated member of E2F family in CRC [23][24][25]. A research reported suppressive function of E2F1 showed that the absence of E2F1 gene lead to an increased incidence and progression of tumorigenesis induced by PTEN loss [23].…”

Section: Discussionmentioning

confidence: 99%

A Research of the Predictive Values of E2F Factors in Colorectal Cancer

Zhang¹,

Yang²,

Zhang³

et al. 2020

Preprint

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“…Transcription factor E2F1 has been reported to play a vital role in cancer stemness, progression, and chemoresistance [46,56,57]. It is well known that E2F1 is overexpressed in several cancers, and upregulated E2F1 is a strong predictor of BC progression, from the superficial to the invasive [48].…”

Section: Discussionmentioning

confidence: 99%

The Long Non-coding RNA TMPO-AS1  Promotes Bladder Cancer Growth and Progression via OTUB1-induced E2F1 Deubiquitination

Zhang

Zhu

Xiao

et al. 2020

Preprint

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BackgroundBladder cancer (BC) is the most common malignant tumor of the urinary system. Increasing evidence indicates long non-coding RNAs (lncRNAs) play crucial roles in cancer tumorigenesis, development, and progression. However, the role of TMPO antisense RNA 1 (TMPO-AS1) is still need to be explored in BC.MethodsThe lncRNA TMPO-AS1 expression was evaluated by bioinformatics analysis and further validated by qRT-PCR. Loss- and gain-of- function assays were performed to determine the biological functions of TMPO-AS1 in BC proliferation, migration, and invasion. Chromatin immunoprecipitation, luciferase reporter assays, western blotting, RNA pull-down, RNA immunoprecipitation assays, and fluorescence in situ hybridization were conducted to explore the molecular mechanisms of TMPO-AS1/E2F transcription factor 1 (E2F1) loop. ResultsTMPO-AS1 is upregulated in bladder cancer and is associated with BC patients’ poor prognoses. Functional experiments demonstrated that TMPO-AS1 promotes bladder cancer cell proliferation, migration, invasion, and inhibits cell apoptosis in vivo and in vitro. Mechanically, E2F1 is responsible for the TMPO-AS1 upregulation. Additionally, TMPO-AS1 facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), leading to E2F1 deubiquitination and stabilization, thereby promotes BC malignant phenotypes. Furthermore, rescue experiments showed that TMPO-AS1 promotes BC growth in an E2F1-dependent manner.ConclusionsOur study is the first to uncover a novel positive regulatory loop of TMPO-AS1/E2F1 important for the promotion of BC malignant behaviors. The TMPO-AS1/E2F1 loop should be considered in the quest for new BC therapeutic options.

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“…Colorectal cancer (CRC) is one of the mostmalignant types of cancers that have been increasing in prevalence on a global scale. Due to its high rate ofmortality, CRC is one of the main causes of cancer deathin the world [1]. Patients with CRC are usually diagnosed with distant metastasis, and the 5-year survival rate is no more than 10% in patients with advanced-stage CRC [2].Over the years, variousstrategiesincluding chemotherapy (i.e., cytotoxic and molecular targeted agents) have been applied to improve the treatment results of patients with CRC [3,4].Despite advances in early detection and treatment, the number of patients with CRC will still grow in the coming decades [5].…”

Section: Introductionmentioning

confidence: 99%

The Role of p53-Mediated Signaling in the Therapeutic Response of Colorectal Cancer to 9F, a Spermine-Modified Naphthalene Diimide Derivative

Gao

Wang

et al. 2020

Cancers

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Colorectal cancer (CRC) is one of the most prevalent cancers due to its frequency and high rate of mortality. Polyamine-vectorized anticancer drugs possess multiple biological properties. Of these drugs, 9F has been shown to inhibit tumor growth and the metastasis of hepatocellular carcinoma. This current study aims to investigate the effects of 9F on CRC and determine its molecular mechanisms of action. Our findings demonstrate that 9F inhibits CRC cell growth by inducing apoptosis and cell cycle arrest, and suppresses migration, invasion and angiogenesis in vitro, resulting in the inhibition of tumor growth and metastasis in vivo. Based on RNA-seq data, further bioinformatic analyses suggest that 9F exerts its anticancer activities through p53 signaling, which is responsible for the altered expression of key regulators of the cell cycle, apoptosis, the epithelial-to-mesenchymal transition (EMT), and angiogenesis. In addition, 9F is more effective than amonafide against CRC. These results show that 9F can be considered as a potential strategy for CRC treatment.

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NFYB-induced high expression of E2F1 contributes to oxaliplatin resistance in colorectal cancer via the enhancement of CHK1 signaling

Cited by 56 publications

References 38 publications

A Research of the Predictive Values of E2F Factors in Colorectal Cancer

A Research of the Predictive Values of E2F Factors in Colorectal Cancer

The Long Non-coding RNA TMPO-AS1  Promotes Bladder Cancer Growth and Progression via OTUB1-induced E2F1 Deubiquitination

The Role of p53-Mediated Signaling in the Therapeutic Response of Colorectal Cancer to 9F, a Spermine-Modified Naphthalene Diimide Derivative

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NFYB-induced high expression of E2F1 contributes to oxaliplatin resistance in colorectal cancer via the enhancement of CHK1 signaling

Cited by 56 publications

References 38 publications

A Research of the Predictive Values of E2F Factors in Colorectal Cancer

A Research of the Predictive Values of E2F Factors in Colorectal Cancer

The Long Non-coding RNA TMPO-AS1&nbsp; Promotes Bladder Cancer Growth and Progression via OTUB1-induced E2F1&nbsp;Deubiquitination

The Role of p53-Mediated Signaling in the Therapeutic Response of Colorectal Cancer to 9F, a Spermine-Modified Naphthalene Diimide Derivative

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The Long Non-coding RNA TMPO-AS1 Promotes Bladder Cancer Growth and Progression via OTUB1-induced E2F1 Deubiquitination