Chk1-induced CCNB1 overexpression promotes cell proliferation and tumor growth in human colorectal cancer

Fang, Yifeng; Yu, Hong; Liang, Xiao; Xu, Jianrong; Cai, Xiujun

doi:10.4161/cbt.29691

Cited by 136 publications

(126 citation statements)

References 34 publications

(37 reference statements)

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“…Among genes coexpressed with the two lncRNAs, for example, CHEK1 encodes checkpoint kinase 1, which belongs to the Serine/Threonine protein kinase family. Previous studies have reported its oncogenic role in several types of human cancer (32)(33)(34)(35). CHEK1 could serve as a biomarker for breast cancer and a therapeutic target for TNBC (36,37).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Triple-Negative Breast Cancer Reveals an Integrated mRNA-lncRNA Signature with Predictive and Prognostic Value

et al. 2016

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While recognized as a generally aggressive disease, triplenegative breast cancer (TNBC) is highly diverse in different patients with variable outcomes. In this prospective observational study, we aimed to develop an RNA signature of TNBC patients to improve risk stratification and optimize the choice of adjuvant therapy. Transcriptome microarrays for 33 paired TNBC and adjacent normal breast tissue revealed tumor-specific mRNAs and long noncoding RNAs (lncRNA) that were associated with recurrence-free survival. Using the Cox regression model, we developed an integrated mRNA-lncRNA signature based on the mRNA species for FCGR1A, RSAD2, CHRDL1, and the lncRNA species for HIF1A-AS2 and AK124454. The prognostic and predictive accuracy of this signature was evaluated in a training set of 137 TNBC patients and then validated in a second independent set of 138 TNBC patients. In addition, we enrolled 82 TNBC patients who underwent taxane-based neoadjuvant chemotherapy (NCT) to further verify the predictive value of the signature. In both the training and validation sets, the integrated signature had better prognostic value than clinicopathologic parameters. We also confirmed the interaction between the administration of taxane-based NCT and different risk groups. In the NCT cohort, patients in the lowrisk group were more likely to achieve pathologic complete remission after taxane-based NCT (P ¼ 0.014). Functionally, we showed that HIF1A-AS2 and AK124454 promoted cell proliferation and invasion in TNBC cells and contributed there to paclitaxel resistance. Overall, our results established an integrated mRNA-lncRNA signature as a reliable tool to predict tumor recurrence and the benefit of taxane chemotherapy in TNBC, warranting further investigation in larger populations to help frame individualized treatments for TNBC patients.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Triple-Negative Breast Cancer Reveals an Integrated mRNA-lncRNA Signature with Predictive and Prognostic Value

et al. 2016

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“…Indeed, induction of CDK1 has been linked to the growth of human colorectal cancer and acute myeloid leukemia [33–34]; the reduction of p27 has been liked to the genesis and progression of a broad array of human cancers, including cancers of the breast, colon, prostate, ovary, lung, stomach, and others [35–37]. The increase of NSun2 levels observed in a variety of human cancers, including those originating in the colon, esophagus, stomach, liver, oral cavity, pancreas, uterus, cervix, prostate, kidney, bladder, thyroid, breast, and skin [25, 38], may be part of a program of senescence repression involving reduced levels of p27.…”

Section: Discussionmentioning

confidence: 99%

NSun2 delays replicative senescence by repressing p27 (KIP1) translation and elevating CDK1 translation

Tang

Fan

Xing

et al. 2015

Aging

100

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A rise in the levels of the cyclin-dependent kinase (CDK) inhibitor p27KIP1 is important for the growth arrest of senescent cells, but the mechanisms responsible for this increase are poorly understood. Here, we show that the tRNA methyltransferase NSun2 represses the expression of p27 in replicative senescence. NSun2 methylated the 5′-untranslated region (UTR) of p27 mRNA at cytosine C64 in vitro and in cells, thereby repressing the translation of p27. During replicative senescence, increased p27 protein levels were accompanied by decreased NSun2 protein levels. Knockdown of NSun2 in human diploid fibroblasts (HDFs) elevated p27 levels and reduced the expression of CDK1 (encoded by CDK1 mRNA, a previously reported target of NSun2), which in turn further repressed cell proliferation and accelerated replicative senescence, while overexpression of NSun2 exerted the opposite effect. Ectopic overexpression of the p27 5′UTR fragment rescued the effect of NSun2 overexpression in lowering p27, increasing CDK1, promoting cell proliferation, and delaying replicative senescence. Our findings indicate that NSun2-mediated mRNA methylation regulates p27 and CDK1 levels during replicative senescence.

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“…CCNB1 gathered the highest connectivity of nodes. CCNB1 inhibition induced colorectal cancer apoptotic death and proliferation in vitro and tumor growth in vivo [32]. Huang L et al found that PBRM1 could block the G2/M transition by repressing cyclin B1, and PBRM1 was associated with advanced tumor stage, low differentiation grade and worse patient outcome [33].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA Expression Profiles for the Characterization of Different Bladder Cancer Grade

Cao

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Bladder cancer (BC) is one of the most frequent urologic tumors worldwide. However, long non-coding RNA(lncRNA) expression profiles in BC progression remain unclear. This study aimed to explore lncRNA expression profiles in different grades of bladder cancer and normal urothelium tissues. Methods: We performed high-throughput sequencing in BC tissues of different grade and obtained the expression profiles of its lncRNAs. Then, aberrantly expressed lncRNAs were validated by quantitative reverse transcription polymerase chain reaction (RT-PCR). Gene Ontology (GO) and pathway analyses were used to investigate the potential function of these lncRNAs. Co-expresson network was constructed to explore the relationship between lncRNAs and target mRNAs. Results: We identified 252 aberrantly expressed lncRNAs in high-grade BC while compared to low-grade BC, and 269 lncRNAs in high-grade BC while compared to normal urothelium. Notably, we found 33 overlapped lncRNAs. Subsequently, 7 lncRNAs were selected from the overlapped part and confirmed by RT-PCR. GO and pathway analyses showed that these dysregulated lncRNAs participated in cell migration, cell adhesion, as well as Ras signaling pathway. Co-expression network and The Cancer Genome Atlas (TCGA) data showed LUCAT1 and CCNB1 had positive relationship in regulating the progress of bladder cancer. Conclusion: Our findings revealed the significant role of lncRNAs in the development process of bladder cancer.

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Chk1-induced CCNB1 overexpression promotes cell proliferation and tumor growth in human colorectal cancer

Cited by 136 publications

References 34 publications

Transcriptome Analysis of Triple-Negative Breast Cancer Reveals an Integrated mRNA-lncRNA Signature with Predictive and Prognostic Value

Transcriptome Analysis of Triple-Negative Breast Cancer Reveals an Integrated mRNA-lncRNA Signature with Predictive and Prognostic Value

NSun2 delays replicative senescence by repressing p27 (KIP1) translation and elevating CDK1 translation

Long Non-Coding RNA Expression Profiles for the Characterization of Different Bladder Cancer Grade

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