Depletion of Aurora A leads to upregulation of FoxO1 to induce cell cycle arrest in hepatocellular carcinoma cells

Lee, Sun-Young; Lee, Gong Rak; Woo, Dong-Hyuk; Park, Neung Hwa; Jeong, Hee; Moon, Yong-Hwan; Han, In-Seob

doi:10.4161/cc.22962

Cited by 33 publications

(29 citation statements)

References 46 publications

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“…FOXO1 was an appealing candidate among thousands of targets due to its diverse roles in controlling cell cycle, apoptosis, stem cells and the aging process (17)(18)(19)(20)(21)(22)(23)27). Previous studies found that FOXO1 function was closely related with its phosphorylation and acetylation modification which determined its transcriptional activity (40)(41)(42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

“…1D and 3), elucidating a novel mechanism of how FOXO1 is aberrantly expressed in breast cancer. As a critical transcription factor, FOXO1 orchestratedly regulates genes involved in cell proliferation, apoptotic response, cell cycle checkpoints and cellular metabolism (17,21,23). We hypothesized that a low level of FOXO1 expression may make these cancers resistant to apoptosis-or differentiation-inducing agents.…”

Section: Discussionmentioning

confidence: 99%

“…Thirteen percent were found to be associated with cell proliferation and cell cycle regulation. Among them, forkhead box O1 (FOXO1) appeared to be an appealing candidate due to its potent roles in regulating the cell cycle, apoptosis, stem cells and the aging process (17)(18)(19)(20)(21)(22)(23). Low and even undetectable FOXO1 expression has been observed in prostate, breast and colon cancers, suggesting its tumor-suppressor role (24)(25)(26)(27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

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Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells

Jin

Yang

et al. 2013

Oncology Reports

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The RNA-binding protein Quaking (QKI) is known to be essential for embryonic development and postnatal myelination. Forkhead box O1 (FOXO1) is a critical tumor suppressor for cell proliferation control. Dysregulation of FOXO1 expression has been observed in a variety of cancers. In the present study, we demonstrated that QKI decreased FOXO1 mRNA expression at the post-transcriptional level. QKI was able to bind the 3'UTR of FOXO1 mRNA directly and decreased its mRNA stability. To determine whether QKI-mediated post-transcriptional repression of FOXO1 indeed plays a role in cancer cells, we first detected both QKI and FOXO1 expression in four breast cancer cell lines. FOXO1 expression was extremely low in these cell lines, whereas QKI expression was relative high. Knockdown of QKI significantly restored FOXO1 expression. ATRA, an inducer of apoptosis or differentiation, dramatically enhanced FOXO1 expression while it repressed QKI expression. Importantly, the ATRA-induced increase in FOXO1 expression was dependent on QKI-mediated post-transcriptional regulation. Consistently, 5-FU, a widely used chemotherapeutic agent, increased FOXO1 expression via inhibition of QKI. In summary, our study provides initial evidence demonstrating that QKI-mediated repression of FOXO1 may be one of the factors contributing to the oncogenesis and progression of breast carcinoma, which suggests that targeting QKI may serve as a novel strategy to sensitize breast cancers to chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells

Jin

Yang

et al. 2013

Oncology Reports

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“…This indicates celecoxib-induced PTEN up-regulation is partially involved in the suppression of hepatic cancer stemness. PTEN is not only upstream regulator of Akt, recent studies indicated other molecular such as Aurora A also regulate Akt pathway [38]. mTOR (a downstream effector of Akt) is also highly activated in aggressive HCC, and mTOR activation plays an important role in hepatoma cell growth and development [39].…”

Section: Discussionmentioning

confidence: 99%

Celecoxib suppresses hepatoma stemness and progression by up-regulating PTEN

et al. 2013

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Celecoxib, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, can prevent several types of cancer, including hepatocellular carcinoma (HCC). Here we show that celecoxib suppressed the self-renewal and drug-pumping functions in HCC cells. Besides, celecoxib depleted CD44 + /CD133 + hepatic cancer stem cells (hCSC). Prostaglandin E2 (PGE2) and CD133 overexpression did not reverse the celecoxib-induced depletion of hCSC. Also, celecoxib inhibited progression of rat Novikoff hepatoma. Moreover, a 60-day celecoxib program increased the survival rate of rats with hepatoma. Histological analysis revealed that celecoxib therapy reduced the abundance of CD44 + /CD133 + hCSCs in hepatoma tissues. Besides, the hCSCs depletion was associated with elevated apoptosis and blunted proliferation and angiogenesis in hepatoma. Celecoxib therapy activated peroxisome proliferator-activated receptor γ (PPARγ) and up-regulated PTEN, thereby inhibiting Akt and disrupting hCSC expansion. PTEN gene delivery by adenovirus reduced CD44/CD133 expression in vitro and hepatoma formation in vivo. This study suggests that celecoxib suppresses cancer stemness and progression of HCC via activation of PPARγ/PTEN signaling.

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“…miR‐101‐5p possibly targets ESR1 , KRAS , CREBBP , FOXO1 and SMAD3 through different pathways. Among them, KRAS , a Kirsten ras oncogene homolog, was reported to have functional synergy with HBx in HCC initiation and progression , and FOXO1 has been proposed to inhibit EMT transcriptional activators in HCC . Additionally, Hishida et al .…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of strand‐specific miRNA‐101‐3p and miRNA‐101‐5p for hepatocellular carcinoma and a bioinformatic analysis of their possible mechanism of action

Yang

Pang

et al. 2017

FEBS Open Bio

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There is accumulating evidence that miRNA might serve as potential diagnostic and prognostic markers for various types of cancer. Hepatocellular carcinoma (HCC) is the most common type of malignant lesion but the significance of miRNAs in HCC remains largely unknown. The present study aimed to establish the diagnostic value of miR‐101‐3p/5p in HCC and then further investigate the prospective molecular mechanism via a bioinformatic analysis. First, the miR‐101 expression profiles and parallel clinical parameters from 362 HCC patients and 50 adjacent non‐HCC tissue samples were downloaded from The Cancer Genome Atlas (TCGA). Second, we aggregated all miR‐101‐3p/5p expression profiles collected from published literature and the Gene Expression Omnibus and TCGA databases. Subsequently, target genes of miR‐101‐3p and miR‐101‐5p were predicted by using the miRWalk database and then overlapped with the differentially expressed genes of HCC identified by natural language processing. Finally, bioinformatic analyses were conducted with the overlapping genes. The level of miR‐101 was significantly lower in HCC tissues compared with adjacent non‐HCC tissues (P < 0.001), and the area under the curve of the low miR‐101 level for HCC diagnosis was 0.925 (P < 0.001). The pooled summary receiver operator characteristic (SROC) of miR‐101‐3p was 0.86, and the combined SROC curve of miR‐101‐5p was 0.80. Bioinformatic analysis showed that the target genes of both miR‐101‐3p and miR‐101‐5p are involved in several pathways that are associated with HCC. The hub genes for miR‐101‐3p and miR‐101‐5p were also found. Our results suggested that both miR‐101‐3p and miR‐101‐5p might be potential diagnostic markers in HCC, and that they exert their functions via targeting various prospective genes in the same pathways.

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Depletion of Aurora A leads to upregulation of FoxO1 to induce cell cycle arrest in hepatocellular carcinoma cells

Cited by 33 publications

References 46 publications

Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells

Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells

Celecoxib suppresses hepatoma stemness and progression by up-regulating PTEN

Diagnostic value of strand‐specific miRNA‐101‐3p and miRNA‐101‐5p for hepatocellular carcinoma and a bioinformatic analysis of their possible mechanism of action

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