Sine oculis homeobox homolog 1 promotes DNA replication and cell proliferation in cervical cancer

Liu, Dan; Zhang, Xiaoxue; Xi, Bixin; Wan, Dongyi; Li, Li; Zhang, Jin; Wang, Wei; Ma, Ding; Wang, Hui; Gao, Qinglei

doi:10.3892/ijo.2014.2510

Cited by 59 publications

(41 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased SIX1 expression resulted in the upregulation of multiple genes related to the initiation of DNA replication. This previous report contained various structural and functional components that represented targets for antineoplastic agents . Such results imply the nuclear matrix, which is the site of many nuclear functions including transcription, replication, the formation of chromatin loops and the control of DNA supercoiling, may be a potential target for cancer therapy …”

Section: Discussionmentioning

confidence: 99%

“…A similar study also found that Sine oculis homeobox homolog 1 (SIX1) functions as a master regulator in the DNA replication of cervical cancer cells. 38 Increased SIX1 expression resulted in the upregulation of multiple genes related to the initiation of DNA replication. This previous report contained various structural and functional components that represented targets for antineoplastic agents.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

DNA primase polypeptide 1 (PRIM1) involves in estrogen‐induced breast cancer formation through activation of the G2/M cell cycle checkpoint

Lee

Chen

Chia‐Jung

et al. 2018

Intl Journal of Cancer

View full text Add to dashboard Cite

The DNA primase polypeptide 1 (PRIM1) is responsible for synthesizing small RNA primers for Okazaki fragments generated during discontinuous DNA replication. PRIM1 mRNA expression levels in breast tumor samples were detected by real-time PCR analysis. Xenografted tumor model was established to study the carcinogenic role of PRIM1 and its potential therapeutic applications. The average PRIM1 mRNA (copy number × 10 /μg) expression was 4.7-fold higher in tumors than in normal tissue (*p = 0.005, n = 254). PRIM1 was detected preferentially at a higher level (>40-fold) in poorly differentiated tumor tissues (n = 46) compared with more highly differentiated tumors tissues (n = 10) (*p = 0.005). Poor overall survival rate was correlated to the estrogen receptor positive (ER+, n = 20) patients with higher PRIM1 expression when compare to the ER- (n = 10) patients (Chi Square test, p = 0.03). Stable expression of PRIM1-siRNA in the ER+ BT-474 cells-xenograft tumors significantly reduced tumor volume in SCID mice (*p = 0.005). The anti-tumoral effects of inotilone isolated from Phellinus linteus was tested and had significant effects on the inhibition of PRIM1 protein expression in ER+ breast cancer cells. In vivo study was performed by administering inotilone (10 mg/kg, twice a week for 6 weeks), which resulted in significantly reduced BT-474-xenografted tumor growth volume compared with control (n =5 per group, *p < 0.05). This study provides evidences for the prognostic effects of PRIM1 with poor overall survival rate in the ER+ patients and will be valuable to test for therapeutic purpose.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DNA primase polypeptide 1 (PRIM1) involves in estrogen‐induced breast cancer formation through activation of the G2/M cell cycle checkpoint

Lee

Chen

Chia‐Jung

et al. 2018

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Based on this finding, we can speculate that the transcriptional regulation of the identified cell cycle genes could depend on the interplay between MYC, MINCR, and one of the members of the Six family of transcription factors. Interestingly, the Six1 protein has recently been found to promote DNA replication and cell proliferation in cervical cancer by regulating the expression of multiple genes related to the initiation of DNA replication (62).…”

Section: Discussionmentioning

confidence: 99%

MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells

Doose¹,

Haake

Bernhart³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Despite the established role of the transcription factor MYC in cancer, little is known about the impact of a new class of transcriptional regulators, the long noncoding RNAs (lncRNAs), on MYC ability to influence the cellular transcriptome. Here, we have intersected RNA-sequencing data from two MYC-inducible cell lines and a cohort of 91 B-cell lymphomas with or without genetic variants resulting in MYC overexpression. We identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated in the same direction by MYC in the model cell lines. Among them, we focused on a lncRNA that we named MYC-induced long noncoding RNA (MINCR), showing a strong correlation with MYC expression in MYC-positive lymphomas. To understand its cellular role, we performed RNAi and found that MINCR knockdown is associated with an impairment in cell cycle progression. Differential gene expression analysis after RNAi showed a significant enrichment of cell cycle genes among the genes down-regulated after MINCR knockdown. Interestingly, these genes are enriched in MYC binding sites in their promoters, suggesting that MINCR acts as a modulator of the MYC transcriptional program. Accordingly, MINCR knockdown was associated with a reduction in MYC binding to the promoters of selected cell cycle genes. Finally, we show that down-regulation of Aurora kinases A and B and chromatin licensing and DNA replication factor 1 may explain the reduction in cellular proliferation observed on MINCR knockdown. We, therefore, suggest that MINCR is a newly identified player in the MYC transcriptional network able to control the expression of cell cycle genes.MYC | lncRNA | cell cycle | B-cell lymphoma M YC is a transcription factor belonging to the basic helixloop-helix zipper family that was originally identified in Burkitt lymphoma (BL) because of a chromosomal translocation that juxtaposes the MYC oncogene with one of three immunoglobulin (Ig) loci (1-3). In BL, the deregulation of the oncogenic transcription factor MYC is considered to be the major driving force in lymphoma development (4, 5). MYC overexpression is not restricted to BL and has been found to be a common feature SignificanceGains of the MYC gene are the most common imbalances in cancer and are associated with poor prognosis, particularly in B-cell lymphoma. Recent advances in DNA sequencing have revealed the existence of thousands of long noncoding RNAs (lncRNAs) with unknown functional relevance. We have here identified a MYC-regulated lncRNA that we named MYC-induced long noncoding RNA (MINCR) that has a strong correlation with MYC expression in cancer. We show that MINCR is functional and controls cell cycle progression by influencing the expression of MYC-regulated cell cycle genes. MINCR is, therefore, a novel player in MYC's transcriptional network, with the potential to open new therapeutic windows in the fight against malignant lymphoma and, possibly, all cancers that rely on MYC expression.

show abstract

“…Formalin-fixed, paraffin-embedded tissue blocks were retrieved from the archive and were analyzed by IHC described previously [21]. In short, The Avidin-Biotin Complex (ABC) Vectastain Kit (Zsgb-Bio, Beijing, China) was used and the DOT1L polyclonal antibody (1:250; ab64077; Abcam), H3K79me2 polyclonal antibody (1:200; ab3594; Abcam), cyclin D3 antibody (1:100; ab63535; Abcam), and the CDK6 polyclonal antibody (1:500; GTX103992; GeneTex) were used as primary antibodies incubated with tissue sections (2 mm) after heat-induced epitope retrieval (10 mM sodium citrate buffer of pH 6.0), followed by incubation with a secondary antibody conjugated to peroxidase (1:100; Dako).…”

Section: Methodsmentioning

confidence: 99%

Prognostic and therapeutic value of disruptor of telomeric silencing-1-like (DOT1L) expression in patients with ovarian cancer

Zhang

Liu

et al. 2017

J Hematol Oncol

Self Cite

View full text Add to dashboard Cite

BackgroundEpigenetics has been known to play a critical role in regulating the malignant phenotype. This study was designed to examine the expression of DOT1L (histone 3 lysine 79 methyltransferase) and H3K79 methylation in normal ovarian tissues and ovarian tumors and to explore the function of DOT1L and its underline mechanisms in ovarian cancer.MethodsThe expression of DOT1L and H3K79 methylation in 250 ovarian tumor samples and 24 normal ovarian samples was assessed by immunohistochemistry. The effects of DOT1L on cell proliferation in vitro were evaluated using CCK8, colony formation and flow cytometry. The DOT1L-targeted genes were determined using chromatin immune-precipitation coupled with high-throughput sequencing (ChIP-seq) and ChIP-PCR. Gene expression levels were measured by real-time PCR and immunoblotting. The effects of DOT1L on tumor growth in vivo were evaluated using an orthotopic ovarian tumor model.ResultsDOT1L expression and H3K79 methylation was significantly increased in malignant ovarian tumors. High DOT1L expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage, histologic grade, and lymphatic metastasis. DOT1L was an independent prognostic factor for the overall survival (OS) and progression-free survival (PFS) of ovarian cancer, and higher DOT1L expression was associated with poorer OS and PFS. Furthermore, DOT1L regulates the transcription of G1 phase genes CDK6 and CCND3 through H3K79 dimethylation; therefore, blocking DOT1L could result in G1 arrest and thereby impede the cell proliferation in vitro and tumor growth in vivo.ConclusionsOur findings first demonstrate that DOT1L over-expression has important clinical significance in ovarian cancer and also clarify that it drives cell cycle progression through transcriptional regulation of CDK6 and CCND3 through H3K79 methylation, suggesting that DOT1L might be potential target for prognostic assessment and therapeutic intervention in ovarian cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0400-8) contains supplementary material, which is available to authorized users.

show abstract

Sine oculis homeobox homolog 1 promotes DNA replication and cell proliferation in cervical cancer

Cited by 59 publications

References 28 publications

DNA primase polypeptide 1 (PRIM1) involves in estrogen‐induced breast cancer formation through activation of the G2/M cell cycle checkpoint

DNA primase polypeptide 1 (PRIM1) involves in estrogen‐induced breast cancer formation through activation of the G2/M cell cycle checkpoint

MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells

Prognostic and therapeutic value of disruptor of telomeric silencing-1-like (DOT1L) expression in patients with ovarian cancer

Contact Info

Product

Resources

About