Krüppel-like factor 4 promotes human osteosarcoma growth and metastasis via regulating CRYAB expression

Zhang, Lu; Zhang, Li; Xia, Xin; He, Sheng‐Wei; He, Hongtao; Zhao, Wenzhi

doi:10.18632/oncotarget.8824

Cited by 31 publications

(32 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With the great genetic scale, high throughput and objectivity, it allows the monitoring of tens of thousands of genes from each patient. As reported previously, HspB5 aggravated the oncogenic transformation[ 18 ]. This is achieved by involving extensive regulatory functions in cell apoptosis, proliferation, migration, invasion, drug resistance, and cell cycle regulation through inhibiting caspase-3 activation[ 19 , 20 ], and anti-VEGF (vascular endothelial growth factor) resistance[ 5 ].…”

Section: Discussionsupporting

confidence: 74%

HspB5 correlates with poor prognosis in colorectal cancer and prompts epithelial-mesenchymal transition through ERK signaling

Wang

Lai

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

Alpha B-crystallin (HspB5) is abnormally expressed in tumor tissues and portends a poor prognosis in cancer patients. However, the role of HspB5 in colorectal cancer (CRC) is still unclear. Seventy CRC patients and 40 healthy volunteers were sampled from August 2012 to March 2015 in order to determine the clinical significance of HspB5. In vitro cellular studies were used to validate its molecular mechanisms in CRC. Our clinical data indicated that HspB5 was up-regulated, and had a positive association with TNM stage CRC patients. The expression level of HspB5 in CRC patients was closely correlated with MMP7 and E-cadherin, two core epithelial–mesenchymal transition (EMT) gene products. The in vitro studies revealed that high HspB5 expression could prompt tumor cell proliferation and invasion, as well as EMT. Gene-microarray analysis suggested three significant signaling pathways (PI3K, p38 and ERK) were involved in HspB5-induced EMT. Signal transduction pathway inhibitors and HspB5 gene knockdown models suggested that HspB5 promotes CRC tumorigenesis and EMT progression through ERK signaling pathways. In summary, HspB5 maybe trigger the EMT in CRC by activating the ERK signaling pathway. It is a potential tumor biomarker for CRC diagnosis and prognosis.

show abstract

Section: Discussionsupporting

confidence: 74%

HspB5 correlates with poor prognosis in colorectal cancer and prompts epithelial-mesenchymal transition through ERK signaling

Wang

Lai

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor that is often overexpressed in human primary OSA tumors compared normal bone and is highly expressed in OSA stem cell populations [ 63 , 64 ]. ShRNA-mediated knockdown of KLF4 in human MG63 and SaOS2 cell lines inhibited cell clonogenicity and abrogated cell migration in wound-healing and Matrigel migration assays and these effects were directly related to downregulation of the KLF4 transcriptional target, CRYAB [ 63 ]. Furthermore, inhibition of KLF4 in human OSA xenografts reduced tumor growth in vivo , providing further support for its role in OSA biology.…”

Section: Discussionmentioning

confidence: 99%

MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines

López

Zhang

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

BackgroundOsteosarcoma (OSA) is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a fundamental role in cancer. The purpose of this study was to investigate the potential contribution of miR-34a loss to the biology of canine OSA, a well-established spontaneous model of the human disease.Methodology and principal findingsRT-qPCR demonstrated that miR-34a expression levels were significantly reduced in primary canine OSA tumors and canine OSA cell lines as compared to normal canine osteoblasts. In canine OSA cell lines stably transduced with empty vector or pre-miR-34a lentiviral constructs, overexpression of miR-34a inhibited cellular invasion and migration but had no effect on cell proliferation or cell cycle distribution. Transcriptional profiling of canine OSA8 cells possessing enforced miR-34a expression demonstrated dysregulation of numerous genes, including significant down-regulation of multiple putative targets of miR-34a. Moreover, gene ontology analysis of down-regulated miR-34a target genes showed enrichment of several biological processes related to cell invasion and motility. Lastly, we validated changes in miR-34a putative target gene expression, including decreased expression of KLF4, SEM3A, and VEGFA transcripts in canine OSA cells overexpressing miR-34a and identified KLF4 and VEGFA as direct target genes of miR-34a. Concordant with these data, primary canine OSA tumor tissues demonstrated increased expression levels of putative miR-34a target genes.ConclusionsThese data demonstrate that miR-34a contributes to invasion and migration in canine OSA cells and suggest that loss of miR-34a may promote a pattern of gene expression contributing to the metastatic phenotype in canine OSA.

show abstract

“…Kruppel like factor 4 (KLF4), a transcription factor associated with carcinogenesis and tumor progression, has opposite effects and mechanisms in different malignancies. KLF4 was upregulated in osteosarcoma and primary breast ductal carcinoma [ 10 , 11 ], but downregulated in lung cancer, gastric cancer, hepatoma, prostate cancer, and renal cell carcinoma suggesting its tumor suppressor role [ 12 – 16 ]. In the present study, we introduced a novel gene activation system (i.e., CRISPR-ON) to activate and overexpress KLF4, and then investigated its effects in bladder carcinogenesis and progression.…”

Section: Introductionmentioning

confidence: 99%

CRISPR-ON-Mediated KLF4 overexpression inhibits the proliferation, migration and invasion of urothelial bladder cancer in vitro and in vivo

Zhu

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Kruppel like factor 4 (KLF4), a transcription factor associated with carcinogenesis and tumor progression, plays an important role in various malignancies. In the present study, we utilized the CRISPR-ON system to upregulate KLF4 expression level and subsequently investigated the effect and mechanism of KLF4 in the carcinogenesis and progression of urothelial bladder cancer (UBC). Immunohistochemistry (IHC) and quantitative RT-PCR (qRT-PCR) were used to evaluate the expression of KLF4. The CpG methylation status of the promoter region was analyzed using bisulfite-sequencing PCR (BSP). CRISPR-ON system comprised sgRNA and dCas9 protein combined with a transcriptional activation domain. The cell proliferation and cell cycle were assessed by CCK-8 assay, flow cytometry and colony formation assay. The cell motility ability was evaluated using trans-well assay. In vivo tumorigenesis assay and lung metastasis model were also performed. The KLF4 expression was significantly downregulated in UBC tissues. The high CpG methylation status in the promoter of KLF4 was confirmed using BSP. KLF4 overexpression was successfully achieved via CRISPR-ON system, which inhibited the proliferation and induced G1-phase arrest in T24 cells through the regulation of AKT/p21 signal. Furthermore, enforced expression of KLF4 also abrogated the migration and invasion of T24 cells by suppressing EMT progression. Finally, in vivo models indicated that the upregulation of KLF4 could inhibit tumorigenesis and lung metastasis in nude mice. In conclusion, KLF4 overexpression mediated by CRISPR-ON inhibits tumorigenesis and EMT progression in UBC cells, representing a potential therapeutic target, and CRISPR-ON system could be a therapeutic strategy for UBC in the future.

show abstract

Krüppel-like factor 4 promotes human osteosarcoma growth and metastasis via regulating CRYAB expression

Cited by 31 publications

References 30 publications

HspB5 correlates with poor prognosis in colorectal cancer and prompts epithelial-mesenchymal transition through ERK signaling

HspB5 correlates with poor prognosis in colorectal cancer and prompts epithelial-mesenchymal transition through ERK signaling

MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines

CRISPR-ON-Mediated KLF4 overexpression inhibits the proliferation, migration and invasion of urothelial bladder cancer in vitro and in vivo

Contact Info

Product

Resources

About