Understanding and Resetting Radiation Sensitivity in Rectal Cancer

Kelley, Katherine A.; Ruhl, Rebecca; Rana, Shushan; Dewey, Elizabeth; Espinosa, Cristina; Thomas, Charles R.; Martindale, Robert G.; Anand, Sudarshan; Tsikitis, Vassiliki L.

doi:10.1097/sla.0000000000002409

Cited by 20 publications

(17 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although gene therapy has brought hopes to NPC patients, it is still in its infancy due to the complex of gene interaction network. CAB39 (calcium-binding protein 39) is an activated factor of STE20 kinase that has been shown involved in the progression of various cancers, including hepatocellular carcinoma, 7 gastric cancer, 8 colorectal cancer, 9 , 10 pancreatic cancer 11 and glioma. 12 – 15 However, its role in NPC is still elusive.…”

Section: Discussionmentioning

confidence: 99%

<p>CAB39 Promotes the Proliferation of Nasopharyngeal Carcinoma CNE-1 Cells via Up-Regulating p-JNK</p>

Peng¹,

Yan²,

Qi³

et al. 2020

CMAR

View full text Add to dashboard Cite

Aim To investigate the role of CAB39 in nasopharyngeal carcinoma (NPC) development and examine its expression level in NPC tumor samples. Methods Immunohistochemistry staining of NPC tissue microarray was conducted to detect the expression of CAB39 protein in NPC tissues, and the clinical significance of CAB39 was evaluated. Lentivirus-mediated over-expression of CAB39 was designed to increase CAB39 expression in CNE-1 cells. Cell colony formation, cell cycle and CCK-8 proliferation experiments were performed to compare the proliferation ability of CNE-1 cells with or without CAB39 over-expression. Western blotting was conducted to examine downstream targets of CAB39. Results CAB39 expression was higher in tumor samples compared to normal tissue and the higher CAB39 expression was positively correlated to higher TNM stage and distant metastasis rate and non-keratinized state. Further, CAB39 over-expression dramatically increased the proliferation and colony formation of CNE-1 cells. Finally, higher p-JNK protein level was found in CAB39 over-expressing cells. Conclusion CAB39 promotes the proliferation of CNE-1 cells via up-regulating p-JNK.

show abstract

Section: Discussionmentioning

confidence: 99%

<p>CAB39 Promotes the Proliferation of Nasopharyngeal Carcinoma CNE-1 Cells via Up-Regulating p-JNK</p>

Peng¹,

Yan²,

Qi³

et al. 2020

CMAR

View full text Add to dashboard Cite

show abstract

“…In situ hybridization was performed on frozen tumor sections as described in our previous studies 45 , 46 using a digoxigenin (DIG)-labeled miR-494 LNA probe (Exiqon). DIG was detected by an anti-DIG horseradish peroxidase antibody (Roche) and amplified using a TSA-Plus Cy3 system (Perkin Elmer).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA regulation of the MRN complex impacts DNA damage, cellular senescence, and angiogenic signaling

et al. 2018

Self Cite

View full text Add to dashboard Cite

MicroRNAs (miRs) contribute to biological robustness by buffering cellular processes from external perturbations. Here we report an unexpected link between DNA damage response and angiogenic signaling that is buffered by a miR. We demonstrate that genotoxic stress-induced miR-494 inhibits the DNA repair machinery by targeting the MRE11a-RAD50-NBN (MRN) complex. Gain- and loss-of-function experiments show that miR-494 exacerbates DNA damage and drives endothelial senescence. Increase of miR-494 affects telomerase activity, activates p21, decreases pRb pathways, and diminishes angiogenic sprouting. Genetic and pharmacological disruption of the MRN pathway decreases VEGF signaling, phenocopies miR-494-induced senescence, and disrupts angiogenic sprouting. Vascular-targeted delivery of miR-494 decreases both growth factor-induced and tumor angiogenesis in mouse models. Our work identifies a putative miR-facilitated mechanism by which endothelial cells can be insulated against VEGF signaling to facilitate the onset of senescence and highlight the potential of targeting DNA repair to disrupt pathological angiogenesis.

show abstract

“…miRs are endogenous, short non-coding, single-stranded RNA spanning approximately 22 nucleotides. We and others have shown that radiation regulated miRs alter DNA damage repair pathways, pro-survival signaling pathways, cell-cycle checkpoint regulation, and apoptosis; functions which radiation therapy exploits for therapeutic gain (19)(20)(21)(22)(23)(24). Our previous work identified a group of miRs regulated in the tumor vasculature in response to radiation (25).…”

Section: Introductionmentioning

confidence: 99%

Differential regulation of microRNA-15a by radiation affects angiogenesis and tumor growth via modulation of acid sphingomyelinase

Rana¹,

Espinosa‐Díez²,

Ruhl³

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

Activation of acid sphingomyelinase (SMPD1) and the generation of ceramide is a critical regulator of apoptosis in response to cellular stress including radiation. Endothelial SMPD1 has been shown to regulate tumor responses to radiation therapy. We show here that the SMPD1 gene is regulated by a microRNA (miR), miR-15a, in endothelial cells (ECs). Standard low dose radiation (2 Gy) upregulates miR-15a and decreases SMPD1 levels. In contrast, high dose radiation (10 Gy and above) decreases miR-15a and increases SMPD1. Ectopic expression of miR-15a decreases both mRNA and protein levels of SMPD1. Mimicking the effects of high dose radiation with a miR-15a inhibitor decreases cell proliferation and increases active Caspase-3 & 7. Mechanistically, inhibition of miR-15a increases inflammatory cytokines, such as IP10, activates caspase-1 inflammasome and increases Gasdermin D, an effector of pyroptosis. Importantly, both systemic and vascular-targeted delivery of miR-15a inhibitor decreases angiogenesis and tumor growth in a CT26 murine colorectal carcinoma model. Taken together, our findings highlight a novel role for miR mediated regulation of SMPD1 during radiation responses and establish proof-of-concept that this pathway can be targeted with a miR inhibitor.

show abstract

Understanding and Resetting Radiation Sensitivity in Rectal Cancer

Abstract: An integrated analysis of rectal cancer miRs may yield biomarkers of radioresistance and offer treatment targets for resensitization.

Cited by 20 publications

References 41 publications

<p>CAB39 Promotes the Proliferation of Nasopharyngeal Carcinoma CNE-1 Cells via Up-Regulating p-JNK</p>

<p>CAB39 Promotes the Proliferation of Nasopharyngeal Carcinoma CNE-1 Cells via Up-Regulating p-JNK</p>

MicroRNA regulation of the MRN complex impacts DNA damage, cellular senescence, and angiogenic signaling

Differential regulation of microRNA-15a by radiation affects angiogenesis and tumor growth via modulation of acid sphingomyelinase

Contact Info

Product

Resources

About