MELK kinase holds promise as a new radiosensitizing target and biomarker in triple-negative breast cancer

Moreno, Carlos S.

doi:10.21037/jtd.2016.10.40

Cited by 6 publications

(2 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Approximately 70% to 80% of BCs express hormone receptors—estrogen receptors, progesterone receptors, or human epidermal growth factor receptor 2 on the cell surface, but about 15% to 20% of BCs are the triple-negative BC (TNBC) subtype, which expresses no hormone receptors [ 1 , 2 ]. Although endocrine therapy is a major treatment option for hormone receptor-positive BCs, no targeted therapies are available for TNBC, which tends to be resistant to chemo- and radiotherapy [ 1 , 3 ]. Therefore, patients with TNBC have higher relapse and mortality rates and worse outcomes than do patients with hormone receptor-positive BC [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

The microRNAs miR-200b-3p and miR-429-5p target the LIMK1/CFL1 pathway to inhibit growth and motility of breast cancer cells

Wang

Song

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) has the worst prognosis of all subtypes of breast cancer (BC), with limited options for conventional therapy and no targeted therapies. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. In this study, we aimed to determine whether two members of the miR-200 family, miR-200b-3p and miR-429-5p, are involved in BC cell proliferation and motility and to elucidate their target genes and pathways. We performed a meta-analysis that reveals down-regulated expression of miR-200b-3p and miR-429-5p in BC tissues and cell lines, consistent with a lower expression of miR-200b-3p and miR-429-5p in MDA-MB-231 and HCC1937 cells than in MCF-7 and MCF-10 cells. Overexpression of miR-200b-3p and miR-429-5p significantly inhibited the proliferation, migration, and invasion of TNBC cells; suppressed the expression of markers for proliferation and metastasis in TNBC cells. We next demonstrated that LIM domain kinase 1 (LIMK1) is a direct target gene of miR-200b-3p and miR-429-5p. Inhibition of LIMK1 reduced the expression and phosphorylation of cofilin 1 (CFL1), which polymerizes and depolymerizes F-actin and G-actin to reorganize cellular actin cytoskeleton. In addition, transfection with mimics for miR-200b-3p and miR-429-5p arrested G2/M and G0/G1 cell cycles respectively, suppressed the expression of the cell cycle–related complexes, cyclin D1/CDK4/CDK6 and cyclin E1/CDK2, in TNBC cells. In conclusion, miR-200b-3p and miR-429-5p suppress proliferation, migration, and invasion in TNBC cells, via the LIMK1/CFL1 pathway. These results provide insight into how specific miRNAs regulate TNBC progression and suggest that the LIMK1/CFL1 pathway is a therapeutic target for treating TNBC.

show abstract

Section: Introductionmentioning

confidence: 99%

The microRNAs miR-200b-3p and miR-429-5p target the LIMK1/CFL1 pathway to inhibit growth and motility of breast cancer cells

Wang

Song

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…MELK is an oncogenic kinase essential for early recurrence of hepatocellular carcinoma (Xia et al, 2016). Studies have shown that MELK is a novel biomarker and a potential therapeutic target in cervical cancer (Lv et al, 2018), triple-negative breast cancer (Moreno, 2016) and gastric cancer (Zhang et al, 2016a). NDC80 (Nuclear division cycle 80) is also known as highly expressed in cancer 1 (HEC1).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis identifies potentially key differentially expressed genes in oncogenesis and progression of clear cell renal cell carcinoma

Zhang

Zou

Yin

et al. 2019

PeerJ

View full text Add to dashboard Cite

Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal types of cancer within the urinary system. Great efforts have been made to elucidate the pathogeny. However, the molecular mechanism of ccRCC is still not well understood. The aim of this study is to identify key genes in the carcinogenesis and progression of ccRCC. The mRNA microarray dataset was downloaded from the Gene Expression Omnibus database. The dataset contains tumor and matched paracancerous specimens from 72 ccRCC patients with clinical stage I to IV. The linear model of microarray data (limma) package in R language was used to identify differentially expressed genes (DEGs). The protein–protein interaction (PPI) network of the DEGs was constructed using the search tool for the retrieval of interacting genes (STRING). Subsequently, we visualized molecular interaction networks by Cytoscape software and analyzed modules with MCODE. A total of 1,284, 1,416, 1,610 and 1,185 up-regulated genes, and 932, 1,236, 1,006 and 929 down-regulated genes were identified from clinical stage I to IV ccRCC patients, respectively. The overlapping DEGs among the four clinical stages contain 870 up-regulated and 645 down-regulated genes. The enrichment analysis of DEGs in the top module was carried out with DAVID. The results showed the DEGs of the top module were mainly enriched in microtubule-based movement, mitotic cytokinesis and mitotic chromosome condensation. Eleven up-regulated genes and one down-regulated gene were identified as hub genes. Survival analysis showed the high expression of CENPE, KIF20A, KIF4A, MELK, NCAPG, NDC80, NUF2, TOP2A, TPX2 and UBE2C, and low expression of ACADM gene could be involved in the carcinogenesis, invasion or recurrence of ccRCC. Literature retrieval results showed the hub gene NDC80, CENPE and ACADM might be novel targets for the diagnosis, clinical treatment and prognosis of ccRCC. In conclusion, the findings of present study may help us understand the molecular mechanisms underlying the carcinogenesis and progression of ccRCC, and provide potential diagnostic, therapeutic and prognostic biomarkers.

show abstract

Structural classification of MELK inhibitors and prospects for the treatment of tumor resistance: A review

Ren¹,

Guo²,

Dong³

et al. 2022

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

MELK kinase holds promise as a new radiosensitizing target and biomarker in triple-negative breast cancer

Cited by 6 publications

References 14 publications

The microRNAs miR-200b-3p and miR-429-5p target the LIMK1/CFL1 pathway to inhibit growth and motility of breast cancer cells

The microRNAs miR-200b-3p and miR-429-5p target the LIMK1/CFL1 pathway to inhibit growth and motility of breast cancer cells

Bioinformatic analysis identifies potentially key differentially expressed genes in oncogenesis and progression of clear cell renal cell carcinoma

Structural classification of MELK inhibitors and prospects for the treatment of tumor resistance: A review

Contact Info

Product

Resources

About