MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly

Tian, Yuan; Hao, Shaobo; Ye, Minhua; Zhang, Anling; Yang, Nan; Wang, Guangxiu; Jia, Zhifan; Yu, Kai; Guo, Lianmei; Pu, Peiyu; Huang, Qiang; Zhong, Yue

doi:10.1016/j.bbrc.2015.01.105

Cited by 34 publications

(31 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…two cell morphology populations were observed. Next, we investigated the influence of CSS on cell morphology, which is closely related to many cell processes, including adhesion, contractility, and migration 21 . To recapitulate GBM migration through the brain parenchyma, cells were grown in a non-confluent monolayer that permitted observation of single cell morphology (Fig.…”

Section: Migration Speed Was Enhanced By Low Css But Decreased By Higmentioning

confidence: 99%

MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility

Calhoun

Cui

Elliott

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Glioblastoma (GBM) is an astrocytic brain tumor with median survival times of <15 months, primarily as a result of high infiltrative potential and development of resistance to therapy (i.e., surgical resection, chemoradiotherapy). A prominent feature of the GBM microenvironment is compressive solid stress (CSS) caused by uninhibited tumor growth within the confined skull. Here, we utilized a mechanical compression model to apply cSS (<115 Pa) to well-characterized LN229 and U251 GBM cell lines and measured their motility, morphology, and transcriptomic response. Whereas both cell lines displayed a peak in migration at 23 Pa, cells displayed differential response to CSS with either minimal (i.e., U251) or large changes in motility (i.e., LN229). Increased migration of LN229 cells was also correlated to increased cell elongation. these changes were tied to epigenetic signaling associated with increased migration and decreases in proliferation predicted via ingenuity ® Pathway Analysis (IPA), characteristics associated with tumor aggressiveness. miRnA-mRnA interaction analysis revealed strong influence of the miR548 family (i.e., mir-548aj, mir-548az, mir-548t) on differential signaling induced by CSS, suggesting potential targets for pharmaceutical intervention that may improve patient outcomes.

show abstract

Section: Migration Speed Was Enhanced By Low Css But Decreased By Higmentioning

confidence: 99%

MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility

Calhoun

Cui

Elliott

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…miRNAs act as post‐transcriptional regulators of gene expression by repressing mRNA translation and/or facilitating mRNA degradation (Lee, ; Ranganathan and Sivasankar, ). Recent studies have shown that let‐7i plays tumor suppressive roles by inhibiting tumor cells’ growth and migration (Fawzy et al ., ; Subramanian et al ., ; Tian et al ., ; Wu et al ., , ; Yang et al ., ; Zhang et al ., ). let‐7i is shown to be downregulated in several cancers including head and neck squamous cell carcinomas (HNSCCs; Liu et al ., ; Roush and Slack, ; Subramanian et al ., ; Yang et al ., ).…”

Section: Introductionmentioning

confidence: 99%

A regulatory BMI1/let‐7i/ERK3 pathway controls the motility of head and neck cancer cells

et al. 2017

View full text Add to dashboard Cite

Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK), whose biological activity is tightly regulated by its cellular abundance. Recent studies have revealed that ERK3 is upregulated in multiple cancers and promotes cancer cell migration/invasion and drug resistance. Little is known, however, about how ERK3 expression level is upregulated in cancers. Here we have identified the oncogenic polycomb group protein BMI1 as a positive regulator of ERK3 level in head and neck cancer cells. Mechanistically, BMI1 upregulates ERK3 expression by suppressing the tumor suppressive microRNA (miRNA) let-7i which directly targets ERK3 mRNA. ERK3 then acts as an important downstream mediator of BMI1 in promoting cancer cell migration. Importantly, ERK3 protein level is positively correlated with BMI1 level in head and neck tumor specimens of human patients. Taken together, our study revealed a molecular pathway consisting of BMI1, miRNA let-7i and ERK3 which controls the migration of head and neck cancer cells, and suggests that ERK3 kinase is a potential new therapeutic target in head and neck cancers, particularly those with BMI1 overexpression.

show abstract

“…IKBKE (also known as IKKε) was originally identified as an oncogene in breast cancer and is overexpressed in approximately 30% of breast carcinomas ( 4 ). IKBKE is also overexpressed in a variety of human cancers and plays important roles in migration, invasion, malignant transformation, poor prognosis, and chemoresistance of cancer cells ( 5 , 6 ). For example, IKBKE was found to be overexpressed in human glioma cells, and down-regulation of IKBKE reduced invasion and migration of the cells ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Co-delivery of IKBKE siRNA and cabazitaxel by hybrid nanocomplex inhibits invasiveness and growth of triple-negative breast cancer

Zhao

Líu

et al. 2020

Sci. Adv.

View full text Add to dashboard Cite

IKBKE is an oncogene in triple-negative breast cancer (TNBC), and we demonstrate that IKBKE small interfering RNA (siRNA) inhibits the proliferation, migration, and invasion of TNBC cells. Despite the recent success of siRNA therapeutics targeting to the liver, there still remains a great challenge to deliver siRNAs to solid tumors. Here, we report a hybrid nanocomplex to co-deliver the IKBKE siRNA and cabazitaxel to TNBC to achieve an optimal antitumor effect. The nanocomplex is modified with hyaluronic acid to target CD44 on TNBC cells. The nanocomplex shows higher cellular uptake and better tumor penetration of the encapsulated cargos. The nanocomplex also exhibits high tumor accumulation and antitumor activity in an orthotopic TNBC mouse model. Encapsulation of cabazitaxel in the nanocomplex enhances the activity of the IKBKE siRNA. The hybrid nanocomplex provides a novel and versatile platform for combination therapies using siRNAs and chemotherapy.

show abstract

MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly

Cited by 34 publications

References 34 publications

MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility

MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility

A regulatory BMI1/let‐7i/ERK3 pathway controls the motility of head and neck cancer cells

Co-delivery of IKBKE siRNA and cabazitaxel by hybrid nanocomplex inhibits invasiveness and growth of triple-negative breast cancer

Contact Info

Product

Resources

About