Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

Samadi, Pouria; Afshar, Saeid; Amini, Razieh; Najafi, Rezvan; Mahdavinezhad, Ali; Pashaki, Abdolazim Sedighi; Gholami, Mohammad Hadi; Saidijam, Massoud

doi:10.1002/jcp.27742

Cited by 36 publications

(23 citation statements)

References 47 publications

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“…Additionally, our study indicated that let-7e inhibition accelerated ovarian cancer tumor growth through promoting the IGF1/ IGF1R/Akt signaling pathway. This was consistent with the result of Pouria Samadi1 and Zhenjun Li, which demonstrated that let-7e targeted IGF1R and modulated the proliferation, migration, and radiosensitivity of colorectal cancer cells (37,38). Future investigations should strive to incorporate let-7e detection into clinical trials to evaluate the value of let-7e for stratification of patients with risk to develop chemoresistance and to relapse.…”

Section: Discussionsupporting

confidence: 87%

Let-7e Suppresses DNA Damage Repair and Sensitizes Ovarian Cancer to Cisplatin through Targeting PARP1

Xiao

Guo

Xie

et al. 2020

Molecular Cancer Research

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Increased DNA damage repair is one of the mechanisms implicated in cisplatin resistance. Our previous study indicated that the deregulation of let-7e promoted cisplatin resistance and that let-7e could suppress DNA double-strand break repair in ovarian cancer. In this study, we further characterized the role of let-7e in DNA damage repair and cisplatin resistance in ovarian cancer, and investigated the underlying mechanisms. The alkaline and neutral comet assay indicated that let-7e impeded both DNA single-and double-strand break repairs through downregulating its target gene PARP1. In vitro and in vivo experiments provided evidence that the let-7e-PARP1-DNA repair axis was involved in the modulation of cisplatin sensitivity in ovarian cancer. Contrary to let-7e, PARP1 was overexpressed in cisplatin-resistant ovarian cancer tissues, and patients with high PARP1 expression exhibited poor progressionfree survival (PFS) and overall survival (OS). Multivariate logistic and Cox regression analyses showed that let-7e and FIGO stage were independent prognostic factors for PFS and OS, whereas let-7e and PARP1 were able to independently predict chemotherapy response. Taken together, our results indicated that low expression of let-7e promoted DNA single-and double-strand break repairs and subsequently contributed to cisplatin resistance by relieving the suppression on PARP1 in ovarian cancer. Implications: Targeting the let-7e-PARP1-DNA repair axis might be an effective strategy for the treatment of chemoresistant ovarian cancer.

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Section: Discussionsupporting

confidence: 87%

Let-7e Suppresses DNA Damage Repair and Sensitizes Ovarian Cancer to Cisplatin through Targeting PARP1

Xiao

Guo

Xie

et al. 2020

Molecular Cancer Research

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“…Increased expression of let-7e-5p in CRC cell lines leads to decreased cell migration and proliferation through targeting the gene coding for serine/threonine kinase DCLK1 [ 41 ], increased sensitivity to treatment with 5-fluorouracil (5FU) and decreased cell invasion through targeting ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 ( ST8SIA1 ) [ 42 ]. let-7e-5p also induces cell cycle arrest through targeting genes encoding insulin-like growth factor 1 receptor ( IGF1R ), which also mediates the decreased sensitivity of CRC cells to both radio- and chemotherapy [ 43 , 44 ].…”

Section: Mirna Clusters Down-regulated In Human Crcmentioning

confidence: 99%

miRNA Clusters with Down-Regulated Expression in Human Colorectal Cancer and Their Regulation

Pidíková

Reis

Herichová

2020

IJMS

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Regulation of microRNA (miRNA) expression has been extensively studied with respect to colorectal cancer (CRC), since CRC is one of the leading causes of cancer mortality worldwide. Transcriptional control of miRNAs creating clusters can be, to some extent, estimated from cluster position on a chromosome. Levels of miRNAs are also controlled by miRNAs “sponging” by long non-coding RNAs (ncRNAs). Both types of miRNA regulation strongly influence their function. We focused on clusters of miRNAs found to be down-regulated in CRC, containing miR-1, let-7, miR-15, miR-16, miR-99, miR-100, miR-125, miR-133, miR-143, miR-145, miR-192, miR-194, miR-195, miR-206, miR-215, miR-302, miR-367 and miR-497 and analysed their genome position, regulation and functions. Only evidence provided with the use of CRC in vivo and/or in vitro models was taken into consideration. Comprehensive research revealed that down-regulated miRNA clusters in CRC are mostly located in a gene intron and, in a majority of cases, miRNA clusters possess cluster-specific transcriptional regulation. For all selected clusters, regulation mediated by long ncRNA was experimentally demonstrated in CRC, at least in one cluster member. Oncostatic functions were predominantly linked with the reviewed miRNAs, and their high expression was usually associated with better survival. These findings implicate the potential of down-regulated clusters in CRC to become promising multi-targets for therapeutic manipulation.

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“…These cell lines have epithelial cell morphology and are rapidly growing lines. [ 22,23 ] The results of the cytotoxicity assay showed that CT26 cells were more sensitive to SORt than HCT116 cells; the IC 50 values were 5.42 and 8.12 μM, respectively. Results of the IC 50 calculation for the anticancer drug regorafenib as positive control were 17.40 and 28.62 μM for CT26 and HCT116 cells, respectively (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

Synthesis, anticancer activity, and β‐lactoglobulin binding interactions of multitargeted kinase inhibitor sorafenib tosylate (SORt) using spectroscopic and molecular modelling approaches

et al. 2020

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Sorafenib tosylate (SORt) is an oral multikinase inhibitor used for treatment of advanced renal cell, liver, and thyroid cancers. In this study, this drug was synthesized and its antiproliferative activities against HCT116 and CT26 cells were assessed. The interaction of SORt with β‐lactoglobulin (BLG) was studied using different fluorescence techniques, circular dichroism (CD), zeta potential measurements, and docking simulation. The results of infrared (IR), mass, HNMR, and CNMR spectra demonstrated that the drug was produced with high quality, purity, and efficiency. SORt showed potent cytotoxicity against HCT116 and CT26 cells with IC50 of 8.12 and 5.42 μM, respectively. For BLG binding of SORt, the results showed that static quenching was the cause of the high affinity drug–protein interaction. Three‐dimensional fluorescence and synchronous spectra indicated that SORt conformation was changed at different levels. CD suggested that the α‐helix content remained almost constant in the BLG–SORt complex, whereas random coil content decreased. Zeta potential values of BLG were more positive after binding with SORt, due to electrostatic interactions between BLG and SORt. Thermodynamic parameters confirmed van der Waals and hydrogen bond interactions in the complex formation. Molecular modelling predicted the presence of hydrogen bonds and electrostatic forces in the BLG–SORt system, which was consistent with the experimental results.

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Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

Cited by 36 publications

References 47 publications

Let-7e Suppresses DNA Damage Repair and Sensitizes Ovarian Cancer to Cisplatin through Targeting PARP1

Let-7e Suppresses DNA Damage Repair and Sensitizes Ovarian Cancer to Cisplatin through Targeting PARP1

miRNA Clusters with Down-Regulated Expression in Human Colorectal Cancer and Their Regulation

Synthesis, anticancer activity, and β‐lactoglobulin binding interactions of multitargeted kinase inhibitor sorafenib tosylate (SORt) using spectroscopic and molecular modelling approaches

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