Inhibition of cisplatin-resistance by RNA interference targeting metallothionein using reducible oligo-peptoplex

Lee, Jong‐Hwan; Chae, Ji-Won; Kim, Jang Kyoung; Kim, Hyung Jin; Chung, Jee Young; Kim, Yong Hee

doi:10.1016/j.jconrel.2015.07.015

Cited by 28 publications

(16 citation statements)

References 18 publications

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“…Numerous genes have been implicated in platinum resistance, such as multidrug resistance protein 2 (MRP2) involved in cisplatin efflux 7 , glutathione and metallothionein involved in platinum detoxification 8 , and excision repair cross-complementation group 1 (ERCC1) involved in DNA damage repair 10 . In this study, TIE1 emerged as a novel sensitizer among other families of genes already shown to affect cisplatin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…Activated cisplatin almost exclusively forms intra-strand platinum-DNA crosslinks and causes DNA damage 5 , blocking cell division and resulting in apoptotic cell death. A wide range of chemo-resistant mechanisms have been identified, including down-regulation of cisplatin uptake 6 , up-regulation of cisplatin excretion 7 and detoxification 8 , down-regulation of ceramide-mediated apoptosis 9 , and increased repair or tolerance of DNA damage 10,11 . Although numerous genes have been implicated in chemo-resistance 12 , the key molecules mediating chemo-resistance remain to be identified.…”

Section: Introductionmentioning

confidence: 99%

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Tyrosine kinase receptor TIE-1 mediates platinum resistance by promoting nucleotide excision repair in ovarian cancer

Ishibashi

Toyoshima

Zhang

et al. 2018

Sci Rep

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Platinum resistance is one of the most challenging problems in ovarian cancer treatment. High-throughput functional siRNA screening identified tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE-1) as a gene that confers cells resistant to cisplatin. Conversely enforced over-expression of TIE-1 was validated to decrease cisplatin sensitivity in multiple ovarian cancer cell lines and up-regulation of TIE-1 was correlated with poor prognosis and cisplatin resistance in patients with ovarian cancer. Mechanistically, TIE-1 up-regulates the nucleotide excision repair (NER) system mediated by xeroderma pigmentosum complementation group C (XPC), thereby leading to decreased susceptibility to cisplatin-induced cell death without affecting cisplatin uptake and excretion. Importantly potentiation of therapeutic efficacy by TIE-1 inhibition was selective to DNA-adduct-type chemotherapeutic platinum reagents. Therefore, TIE-1 is suggested to promote XPC-dependent NER, rendering ovarian cancer cells resistant to platinum. Accompanied with novel findings, TIE-1 could represent as a novel therapeutic target for platinum-resistant ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tyrosine kinase receptor TIE-1 mediates platinum resistance by promoting nucleotide excision repair in ovarian cancer

Ishibashi

Toyoshima

Zhang

et al. 2018

Sci Rep

View full text Add to dashboard Cite

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“…Additionally, in vivo tumor models showed synergistically enhanced the tumor-suppressive effects of co-administration of shMT/rPOA oligopeptoplex and cisplatin. These results demonstrated that MT overexpression was at least one of the main reasons for cisplatin resistance [ 102 ]. Upregulation of MTs was shown to increase irinotecan resistance in gastric cancer patients [ 103 ].…”

Section: Introductionmentioning

confidence: 99%

“…Lai et al reported that silencing the MT2A gene by siRNAs induced entosis (the internalization of a cell into another cell) [ 162 ] in breast cancer, and this result may provide new insights into strategies to limit tumor cell growth [ 163 ]. Similarly, Lee et al used shMT/rPOA oligopeptoplexes to downregulate MT expression and reverse the cisplatin resistance and verified enhanced anticancer efficacy in both cisplatin-resistant cell lines and in vivo mouse cancer models [ 102 ]. Antisense approaches targeting unique mRNA molecules are intended to reduce the expression of specific proteins, and this strategy is possibly applicable for cancer therapy [ 164 ].…”

Section: Introductionmentioning

confidence: 99%

The roles of metallothioneins in carcinogenesis

2018

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Metallothioneins (MTs) are small cysteine-rich proteins that play important roles in metal homeostasis and protection against heavy metal toxicity, DNA damage, and oxidative stress. In humans, MTs have four main isoforms (MT1, MT2, MT3, and MT4) that are encoded by genes located on chromosome 16q13. MT1 comprises eight known functional (sub)isoforms (MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1M, and MT1X). Emerging evidence shows that MTs play a pivotal role in tumor formation, progression, and drug resistance. However, the expression of MTs is not universal in all human tumors and may depend on the type and differentiation status of tumors, as well as other environmental stimuli or gene mutations. More importantly, the differential expression of particular MT isoforms can be utilized for tumor diagnosis and therapy. This review summarizes the recent knowledge on the functions and mechanisms of MTs in carcinogenesis and describes the differential expression and regulation of MT isoforms in various malignant tumors. The roles of MTs in tumor growth, differentiation, angiogenesis, metastasis, microenvironment remodeling, immune escape, and drug resistance are also discussed. Finally, this review highlights the potential of MTs as biomarkers for cancer diagnosis and prognosis and introduces some current applications of targeting MT isoforms in cancer therapy. The knowledge on the MTs may provide new insights for treating cancer and bring hope for the elimination of cancer.

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“…Fueled by recent advances in moving siRNA therapeutics from bench to clinics [ 28 ], possible therapeutic strategy can also be developed by suppressing miR-216a expression. It should be noted that cisplatin resistance may also be ascribed to other mechanisms, such as reduced accumulation of the drug [ 29 ], increased levels of metallothionein [ 30 ] and gluotathione [ 31 ], as well as enhanced DNA repair [ 32 ]. Gene predisposition, such as BRCA1 and BRCA2 mutation, also contributes significantly to ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

STAT3 regulated miR-216a promotes ovarian cancer proliferation and cisplatin resistance

2018

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Cisplatin is the first-line treatment for ovarian cancer. However, the clinical outcome of cisplatin treatment in ovarian cancer is hindered by cancer resistance. Here we aim to explore the role and mechanism of miR-216a in the cisplatin resistance of ovarian cancer. The effects of miR-216a overexpression and inhibition on ovarian cell proliferation, colony formation, and cisplatin resistance were investigated by MTT assay and soft agar colony formation assay. Bioinformatics analyses using TargetScan and rVista, qPCR, and luciferase assay were also used to explore and verify downstream effectors and regulators of miR-216a. Proliferation, colony formation, and cisplatin resistance of ovarian cancer cells are promoted by miR-216a overexpression but inhibited by miR-216a inhibition. PTEN is a direct target of miR-216a and PTEN expression antagonizes the tumor-promoting function of miR-216a. STAT3 is a regulator of miR-216a, and PTEN is also regulated by STAT3. miR-216a up-regulation is associated with cisplatin resistance in ovarian cancer and this effect is mediated by PTEN. STAT3 is a regulator of miR-216a. Strategies that inhibit miR-216a is a potential strategy for overcoming the cisplatin resistance in ovarian cancer.

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Inhibition of cisplatin-resistance by RNA interference targeting metallothionein using reducible oligo-peptoplex

Cited by 28 publications

References 18 publications

Tyrosine kinase receptor TIE-1 mediates platinum resistance by promoting nucleotide excision repair in ovarian cancer

Tyrosine kinase receptor TIE-1 mediates platinum resistance by promoting nucleotide excision repair in ovarian cancer

The roles of metallothioneins in carcinogenesis

STAT3 regulated miR-216a promotes ovarian cancer proliferation and cisplatin resistance

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