miR-122 Targets X-Linked Inhibitor of Apoptosis Protein to Sensitize Oxaliplatin-Resistant Colorectal Cancer Cells to Oxaliplatin-Mediated Cytotoxicity

Hua, Yi-Jun; Zhu, Yuqing; Zhang, Jijie; Zhu, Zhenfeng; Ning, Zhouyu; Chen, Hao; Liu, Luming; Chen, Zhen; Meng, Zhiqiang

doi:10.1159/000495832

Cited by 32 publications

(20 citation statements)

References 30 publications

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“…Oxaliplatin, which is commonly used for CRC treatment, binds covalently to DNA nucleobases to form guanine–guanine and guanine–adenine DNA links [4]. This abnormal binding interferes with the structure of DNA and inhibits DNA replication, repair, and transcription, triggering double-strand breaks and causing apoptosis [5].…”

Section: Discussionmentioning

confidence: 99%

“…For chemotherapy, either FOLFOX (5-fluorouracil and leucovorin with oxaliplatin) or FOLFIRI (5-fluorouracil, leucovorin with irrinotecan) combined with bevacizumab is mainly used [3]. Despite advances in treatment strategies for CRC, the prognosis remains poor because of the high rates of metastasis [4]. Oxaliplatin is the first platinum-based drug to demonstrate clinical effectiveness against CRC, and it remains one of the most effective chemotherapeutic drug for CRC treatment along with 5-fluorouracil and leucovorin [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Despite advances in treatment strategies for CRC, the prognosis remains poor because of the high rates of metastasis [4]. Oxaliplatin is the first platinum-based drug to demonstrate clinical effectiveness against CRC, and it remains one of the most effective chemotherapeutic drug for CRC treatment along with 5-fluorouracil and leucovorin [4,5]. However, repeated and long-term administration induces drug resistance through the promotion of export from the cells and nucleotide excision repair by increasing expression of the multidrug resistance protein, glutathione, and excision repair cross-complementation group 1 [6,7].…”

Section: Introductionmentioning

confidence: 99%

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Cannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer Cells

Jeong

Kim

et al. 2019

Cancers

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Although oxaliplatin is an effective chemotherapeutic drug for colorectal cancer (CRC) treatment, patients often develop resistance to it. Therefore, a new strategy for CRC treatment is needed. The purpose of this study was to determine the effect of cannabidiol (CBD), one of the components of the cannabis plant, in overcoming oxaliplatin resistance in CRC cells. We established oxaliplatin-resistant cell lines, DLD-1 R and colo205 R, in CRC DLD-1 and colo205 cells. Autophagic cell death was induced when oxaliplatin-resistant cells were treated with both oxaliplatin and CBD. Additionally, phosphorylation of nitric oxide synthase 3 (NOS3) was increased in oxaliplatin-resistant cells compared to that in parent cells. Combined treatment with oxaliplatin and CBD reduced phospho-NOS3 levels and nitric oxide (NO) production and resulted in the production of reactive oxygen species (ROS) by reducing the levels of superoxide dismutase 2, an antioxidant present in the mitochondria, causing mitochondrial dysfunction. Taken together, these results suggest that elevated phosphorylation of NOS3 is essential for oxaliplatin resistance. The combination of oxaliplatin and CBD decreased NOS3 phosphorylation, which resulted in autophagy, by inducing the overproduction of ROS through mitochondrial dysfunction, thus overcoming oxaliplatin resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer Cells

Jeong

Kim

et al. 2019

Cancers

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“…4,5 But since intrinsic or acquired resistance to L-OHP has affected its chemotherapeutic sensitivity, reversing the L-OHP resistance of the CRC is a practical method for enhancing chemosensitivity. 6,7 The outer membrane of gram-negative bacteria is made up of Lipopolysaccharide (LPS). 8 The potential use of bacteria or endotoxins of the effects of anti-tumor has been widely researched for decades.…”

Section: Introductionmentioning

confidence: 99%

<p>LPS Enhances the Chemosensitivity of Oxaliplatin in HT29 Cells via GSDMD-Mediated Pyroptosis</p>

Liu

Wang

et al. 2020

CMAR

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Introduction: Pyroptosis induced by lipopolysaccharide (LPS) is a dissolved form of cell death. The molecular marker gasdermin D, specifically GSDMD-N, is critically required for the induction of pyroptosis. Recently, there have been studies showing that LPS is closely related to tumor biology. Methods: Specimens from 40 patients with colorectal cancer (CRC) were collected. Eight-to twelve-week-old C57BL6 male mice (n=30) were raised. Immunohistochemistry and Western blot were performed to test the expression of GSDMD. Moreover, cytotoxicity assay, IL-18 and IL-1β ELISA, Annexin V and PI stain, and wound healing assay were also made. Gene Expression Profiling Interactive Analysis (GEPIA) was used to verify the expression of GSDMD and overall survival of CRC patients with a high/low expression of GSDMD. Results: In the research, we showed that the poor prognosis in CRC patients was significantly related to the GSDMD expression and significantly down-regulated in human colorectal cancer (CRC) tissues. Treatment with LPS, but not TNF-α, induced pyroptosis via promoting the expression of GSDMD and GSDMD-N membrane translocation and enhanced chemosensitivity in response to L-OHP in HT29 cells. Furthermore, the enforced expression of GSDMD in HT29 cells reduced cell survival and induced cell death. Discussion: These results of studies suggest that the low expression of GSDMD correlates with a poor CRC prognosis, and that pyroptosis induced by LPS may improve the anti-cancer effect of L-OHP, inhibiting the tumorigenesis of CRC by activating GSDMD. Our findings lay the foundation for further development of GSDMD serving as an important prognostic biomarker and a valid CRC therapeutic target.

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“…Restoring miRNA-122 levels in these cell lines resulted in increased sensitivity to oxaliplatin [135].…”

Section: Mirna-122 Influences Treatment Sensitivity In Colorectal Canmentioning

confidence: 99%

MiRNAs as Novel Adipokines: Obesity-Related Circulating MiRNAs Influence Chemosensitivity in Cancer Patients

Withers

Dewhurst

Hammond

et al. 2020

ncRNA

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Adipose tissue is an endocrine organ, capable of regulating distant physiological processes in other tissues via the release of adipokines into the bloodstream. Recently, circulating adipose-derived microRNAs (miRNAs) have been proposed as a novel class of adipokine, due to their capacity to regulate gene expression in tissues other than fat. Circulating levels of adipokines are known to be altered in obese individuals compared with typical weight individuals and are linked to poorer health outcomes. For example, obese individuals are known to be more prone to the development of some cancers, and less likely to achieve event-free survival following chemotherapy. The purpose of this review was twofold; first to identify circulating miRNAs which are reproducibly altered in obesity, and secondly to identify mechanisms by which these obesity-linked miRNAs might influence the sensitivity of tumors to treatment. We identified 8 candidate circulating miRNAs with altered levels in obese individuals (6 increased, 2 decreased). A second literature review was then performed to investigate if these candidates might have a role in mediating resistance to cancer treatment. All of the circulating miRNAs identified were capable of mediating responses to cancer treatment at the cellular level, and so this review provides novel insights which can be used by future studies which aim to improve obese patient outcomes.

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miR-122 Targets X-Linked Inhibitor of Apoptosis Protein to Sensitize Oxaliplatin-Resistant Colorectal Cancer Cells to Oxaliplatin-Mediated Cytotoxicity

Cited by 32 publications

References 30 publications

Cannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer Cells

Cannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer Cells

<p>LPS Enhances the Chemosensitivity of Oxaliplatin in HT29 Cells via GSDMD-Mediated Pyroptosis</p>

MiRNAs as Novel Adipokines: Obesity-Related Circulating MiRNAs Influence Chemosensitivity in Cancer Patients

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