Targeting CDK6 in cancer: State of the art and new insights

Tadesse, Solomon; Yu, Mingfeng; Kumarasiri, Malika; Le, Bich Thuy; Wang, Shudong

doi:10.1080/15384101.2015.1084445

Cited by 120 publications

(89 citation statements)

References 120 publications

(146 reference statements)

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“…CDK6 upregulation is found in many cancers, including lymphoma, leukemia, bladder cancer, pancreatic cancer, and prostate cancer, as has been reviewed elsewhere. [104] In the brain, increased CDK6 expression can be found in malignant glioma and medulloblastoma. [105][106][107] CDK6 expression in gliomas increases with higher tumor grade and is correlated with a worse prognosis.…”

Section: Cdk6 Is Mutated In Primary Microcephaly and Upregulated In Gmentioning

confidence: 99%

A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?

Lang

Gershon

2018

BioEssays

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New targets for brain tumor therapies may be identified by mutations that cause hereditary microcephaly. Brain growth depends on the repeated proliferation of stem and progenitor cells. Microcephaly syndromes result from mutations that specifically impair the ability of brain progenitor or stem cells to proliferate, by inducing either premature differentiation or apoptosis. Brain tumors that derive from brain progenitor or stem cells may share many of the specific requirements of their cells of origin. These tumors may therefore be susceptible to disruptions of the protein products of genes that are mutated in microcephaly. The potential for the products of microcephaly genes to be therapeutic targets in brain tumors are highlighted hereby reviewing research on EG5, KIF14, ASPM, CDK6, and ATR. Treatments that disrupt these proteins may open new avenues for brain tumor therapy that have increased efficacy and decreased toxicity.

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Section: Cdk6 Is Mutated In Primary Microcephaly and Upregulated In Gmentioning

confidence: 99%

A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?

Lang

Gershon

2018

BioEssays

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“…The above results of the cell cycle assay showed that HOST2 regulated the G 1 /S phase in cells. Through a literature review, it was noted that CDK6 is a major G 0 /G 1 checkpoint regulator and frequently deregulated in cancer cells (27); the expression of CDK6 has been associated with poor survival outcomes and is considered to be a promising therapeutic target for TNBC (28). The results suggested that CDK6 was a key regulator in the G 1 /S phase and is pivotal in the progression of TNBC.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of long non-coding RNA HOST2 inhibits the�proliferation of triple negative breast cancer via regulation of the let-7b/CDK6 axis

Yuedong¹,

Zhang²,

Kang³

et al. 2018

Int J Mol Med

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The upregulation of long non-coding RNA (lncRNA) human ovarian cancer-specific transcript 2 (HOST2) has been identified in breast cancer. The present study aimed to investigate whether lncRNA HOST2 regulated the proliferation of triple negative breast cancer (TNBC) cells, and the underlying molecular mechanism. In total, 30 patients with primary TNBC, who were treated at Wuhai People's Hospital (Wuhai, China), were recruited for the present study. Reverse transcription-quantitative polymerase chain reaction analysis was used for the examination of gene expression levels. A Cell Counting kit-8 (CCK-8) assay was used for the detection of cell proliferation. Phases of the cell cycle were evaluated by flow cytometry. Western blot analysis was performed to detect protein expression levels. A dual luciferase activity assay was performed to examine the interaction between microRNA (miRNA) and the 3' untranslated region (UTR) of target mRNA. The results revealed increased expression levels of HOST2 in tumor tissues from patients with TNBC. A positive correlation was identified between the expression of HOST2 and cyclin-dependent kinase 6 (CDK6) in tumor tissues. The silencing of HOST2 induced cell proliferation inhibition and cell cycle redistribution in MDA-MB-231 and MDA-MB-468 TNBC cells. In these two cell lines, HOST2 silencing caused a decrease in the phosphorylation of RB1 and CDK6, which was observed at the mRNA and protein levels. However, the silencing of CDK6 did not alter the expression of HOST2. It was hypothesized and confirmed that let-7b, a previously reported target miRNA of HOST2, was able to directly bind to the 3'UTR of CDK6 and repress its expression. The expression of let-7b was negatively correlated with the expression of HOST2 and CDK6 in tumor tissues. Overall, the data suggested that lncRNA HOST2 acts as an oncogene in TNBC via the upregulation of CDK6.

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“…Among all the members, CDK1, CDK2, CDK4 and CDK6 are implicated in cell cycle regulation while CDKs7‐11 are relevant to transcription (Malumbres & Barbacid, ). The enzymatic activity of CDKs can be stimulated by binding to cyclins and the deregulation of this function is a hallmark of several diseases, including cancer (Tadesse, Yu, Kumarasiri, Le, & Wang, ). Previous research has elucidated that the disorder of CDKs may lead to the malignant proliferation of tumor cells and tumorigenesis (Malumbres & Barbacid, ; Tadesse et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…The enzymatic activity of CDKs can be stimulated by binding to cyclins and the deregulation of this function is a hallmark of several diseases, including cancer (Tadesse, Yu, Kumarasiri, Le, & Wang, ). Previous research has elucidated that the disorder of CDKs may lead to the malignant proliferation of tumor cells and tumorigenesis (Malumbres & Barbacid, ; Tadesse et al, ). Cyclin‐dependent kinase 6 (CDK6) is a member of CDK family, which has been identified not only as a CDK but a transcriptional regulator (Kollmann et al, ; Uras et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…Cyclin‐dependent kinase 6 (CDK6) is a member of CDK family, which has been identified not only as a CDK but a transcriptional regulator (Kollmann et al, ; Uras et al, ). CDK6 is responsible for G1 to S cell‐cycle regulation and cell differentiation, and the abnormal expression pattern of this gene has been reported in diverse cancers, such as colorectal carcinoma, medulloblastoma, and oral squamous cell carcinomas (Andisheh‐Tadbir, Ashraf, & Jeiroodi, ; Tadesse et al, ). Specifically, CDK6 has been recognized as a novel transcriptional regulator in acute lymphoid leukemia and acute myeloid leukemia.…”

Section: Introductionmentioning

confidence: 99%

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CDK6 3'UTR polymorphisms alter the susceptibility to cervical cancer among Uyghur females

Aierken

Dong

Abulimiti

et al. 2019

Molec Gen & Gen Med

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Aims Cyclin dependent kinase 6 (CDK6) plays a crucial role in malignant tumor whereas less is reported in cervical cancer development. The aim of this study was to evaluate the effects of CDK6 3' untranslated region (3'UTR) polymorphisms on cervical cancer susceptibility among Uyghur females. Methods The genotypes of the six CDK6 variants (rs8179, rs42032, rs42033, rs42034, rs42035, and rs42038) were identified among 306 cervical cancer cases and 310 healthy controls with the Agena MassARRAY platform. The associations of the candidate single nucleotide polymorphisms (SNPs) with the cervical cancer risk were evaluated under genetic models using conditional logistic regression analysis. Bioinformatics analysis was performed for SNP function prediction with the online databases. The expression differences between tumor tissues and normal cervix samples were also examined by Real‐time PCR. Results CDK6 rs8179 and rs42033 were correlated to the decreased risk of cervical cancer in Uyghurs under the allele model (rs8179 and rs42033: OR = 0.60, 95% CI: 0.37–0.99, p = 0.043) and log‐additive model (rs8179 and rs42033: OR = 0.62, 95% CI: 0.38–1.00, p = 0.047). Rs8179, rs42032, and rs42033 were associated with susceptibility to high‐grade cervical cancer in different genetic models as well ( p < 0.05). Dataset‐based analysis also uncovered the potential effects of these significant SNPs. In addition, aberrant expression of CDK6 were detected in cervical tumors. Conclusions Our results suggested the relationships between CDK6 3'UTR polymorphisms and cervical cancer pathogenesis, and the involvement of CDK6 in cervical cancer development among Uyghur females.

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Targeting CDK6 in cancer: State of the art and new insights

Cited by 120 publications

References 120 publications

A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?

A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?

Knockdown of long non-coding RNA HOST2 inhibits the�proliferation of triple negative breast cancer via regulation of the let-7b/CDK6 axis

CDK6 3'UTR polymorphisms alter the susceptibility to cervical cancer among Uyghur females

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