FXR1 promotes the malignant biological behavior of glioma cells via stabilizing MIR17HG

Cao, Shuo; Zheng, Jian; Liu, Xiaobai; Liu, Yunhui; Ruan, Xuelei; Ma, Jun; Liu, Libo; Wang, Di; Yang, Chunqing; Cai, Heng; Li, Zhen; Feng, Ziyi; Xue, Yixue

doi:10.1186/s13046-018-0991-0

Cited by 61 publications

(47 citation statements)

References 53 publications

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“…Another report showed that FXR1 promotes the malignant biological behavior of glioma cells by stabilizing MIR17HG [12]. However, we did not find any correlation between Such studies on inhibiting FXR1 for therapeutic purposes are currently undergoing in our laboratory.…”

contrasting

confidence: 78%

“…The major biological functions of RBPs include regulation of RNA stability, splicing, and translation [9]. Recent studies have shown that FXR1 is a key promoter of tumor progression, which is critical for the growth of many cancers such as non-small cell lung cancer (NSCLC) [10], prostate cancer [11], glioma [12], and oral squamous cell carcinoma (OSCC) [13]. It has been reported that FXR1 binds to AU-rich elements (AREs) within the 3′untranslated region (3′UTR) and enhances the stability of TNF-α and COX2 mRNAs [14,15].…”

Section: Introductionmentioning

confidence: 99%

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RNA-binding protein FXR1 drives cMYC translation by mRNA circularization through eIF4F recruitment in ovarian cancer

George¹,

Parashar³

et al. 2020

Preprint

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FXR1 (Fragile X-Related protein 1) gene encodes an RNA binding protein, which is highly amplified or copy-gained in ovarian cancer. We found that amplification and copy-gain of FXR1 increased the expression of FXR1 mRNA and FXR1 protein in ovarian cancer patients and associated with poor prognosis. FXR1 improved cells proliferation and tumor growth, while depletion of FXR1 induced apoptosis and reduced tumor growth both in vitro and in vivo. Through reverse phase protein array (RPPA) we identified that cMYC is the direct target of FXR1 in ovarian cancer cells. Our study demonstrated that FXR1 binds to the AU rich elements (ARE) presents within the 3 untranslated region (UTR) of cMYC. We found that FXR1 binding on UTR leads to the circularization of mRNA through the recruitment of eukaryotic translation initiation factors (eIFs) to the translation start site for cMYC translation. Altogether, our study provides novel evidence on the mechanism how cMYC is regulated by FXR1 CNV in cancer cells for tumor progression.

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confidence: 78%

Section: Introductionmentioning

confidence: 99%

RNA-binding protein FXR1 drives cMYC translation by mRNA circularization through eIF4F recruitment in ovarian cancer

George¹,

Parashar³

et al. 2020

Preprint

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“…Schulte JH et al reported that miR-17-92 cluster ampli cation in neuroblastomas was associated with a poor prognosis [21]. lncRNA MIR17HG was upregulated in glioma tissues and cell lines, and acted as competing endogenous RNA (ceRNA) to sponge miR-346/miR-425-5p in regulating the malignant of glioma [14]. Yuze Cao et al reported that lncRNA MIR17HG-mediated ceRNA network was identi ed as a potential prognostic biomarker for glioblastoma [22].…”

Section: Discussionmentioning

confidence: 99%

Genetic variants in MIR17HG affect the susceptibility and prognosis of glioma in a Chinese Han population

Feng

Ouyang

et al. 2020

Preprint

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Background: lncRNA MIR17HG was upregulated in glioma, and participated in promoting proliferation, migration and invasion of glioma. However, the role of MIR17HG polymorphisms in the occurrence and prognosis of glioma is still unclear.Methods: In the study, 592 glioma patients and 502 control subjects were recruited. Agena MassARRAY platform was used to detect the genotype of MIR17HG polymorphisms. Logistic regression analysis was used to evaluate the relationship between MIR17HG single nucleotide polymorphisms (SNPs) and glioma risk by odds ratio (OR) and 95% confidence intervals (CIs). Kaplan–Meier curves, Cox hazards models were performed for assessing the role of these SNPs in glioma prognosis by hazard ratios (HR) and 95% CIs.Results: We found that rs7318578 (OR = 2.25, p = 3.18´10-5) was significantly associated with glioma susceptibility in the overall participants. In the subgroup with age < 40 years, rs17735387 (OR = 1.53, p = 9.05´10-3) and rs7336610 (OR = 1.35, p = 0.016) were related to the higher glioma susceptibility. More importantly, rs17735387 (HR = 0.82, log-rank p = 0.026) were associated with the longer survival of glioma patients. The GA genotype of rs17735387 had a better overall survival (HR = 0.75, log-rank p = 0.013) and progression free survival (HR = 0.73, log-rank p = 0.032) in patients with Ⅰ-Ⅱ glioma. We also found that rs72640334 was related to the poor prognosis (HR = 1.49, Log-rank p = 0.035) in female patients. In the subgroup of patients with age ³ 40 years, rs17735387 was associated with a better prognosis (HR = 0.036, Log-rank p = 0.002).Conclusion: Our study firstly reported that MIR17HG rs7318578 was a risk factor for glioma susceptibility and rs17735387 was associated with the longer survival of glioma among Chinese Han population, which might help to enhance the understanding of MIR17HG gene in gliomagenesis.

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“…Many different types of brain cancers have been characterized, and in almost all of them, BHLHE40 expression has been shown to be higher than in surrounding non-tumor tissue. BHLHE40 was upregulated in glioma compared to non-tumor brain tissue and played an oncogenic role in glioma cells [73].…”

Section: Brain Tumorsmentioning

confidence: 96%

Non-circadian aspects of BHLHE40 cellular function in cancer

2020

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While many genes specifically act as oncogenes or tumor suppressors, others are tumor promoters or suppressors in a context-dependent manner. Here we will review the basic-helix-loop-helix (BHLH) protein BHLHE40, (also known as BHLHB2, STRA13, DEC1, or SHARP2) which is overexpressed in gastric, breast, and brain tumors; and downregulated in colorectal, esophageal, pancreatic and lung cancer. As a transcription factor, BHLHE40 is expressed in the nucleus, where it binds to target gene promoters containing the E-box hexanucleotide sequence, but can also be expressed in the cytoplasm, where it stabilizes cyclin E, preventing cyclin E-mediated DNA replication and cell cycle progression. In different organs BHLHE40 regulates different targets; hence may have different impacts on tumorigenesis. BHLHE40 promotes PI3K/Akt/ mTOR activation in breast cancer, activating tumor progression, but suppresses STAT1 expression in clear cell carcinoma, triggering tumor suppression. Target specificity likely depends on cooperation with other transcription factors. BHLHE40 is activated in lung and esophageal carcinoma by the tumor suppressor p53 inducing senescence and suppressing tumor growth, but is also activated under hypoxic conditions by HIF-1α in gastric cancer and hepatocellular carcinomas, stimulating tumor progression. Thus, BHLHE40 is a multi-functional protein that mediates the promotion or suppression of cancer in a context dependent manner.

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FXR1 promotes the malignant biological behavior of glioma cells via stabilizing MIR17HG

Cited by 61 publications

References 53 publications

RNA-binding protein FXR1 drives cMYC translation by mRNA circularization through eIF4F recruitment in ovarian cancer

RNA-binding protein FXR1 drives cMYC translation by mRNA circularization through eIF4F recruitment in ovarian cancer

Genetic variants in MIR17HG affect the susceptibility and prognosis of glioma in a Chinese Han population

Non-circadian aspects of BHLHE40 cellular function in cancer

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