MicroRNAs and colorectal cancer chemoresistance: New solution for old problem

Vaghari‐Tabari, Mostafa; Majidinia, Maryam; Moein, Soheila; Qujeq, Durdi; Asemi, Zatollah; Alemi, Forough; Mohamadzadeh, Ramin; Targhazeh, Nilofar; Safa, Amin; Yousefi, Bahman

doi:10.1016/j.lfs.2020.118255

Cited by 49 publications

(34 citation statements)

References 149 publications

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“…Transport based cellular mechanisms of drug resistance have been shown to be one of the most understood modes of resistance in CRC [12,17,18,20,21]. It mainly refers to the efflux of drugs out of cancer cells through different membrane transporters, thus resulting in decreased intracellular accumulation of anticancer drugs and chemotherapy failure.…”

Section: Drug Resistance In Crcmentioning

confidence: 99%

“…ABC transporters are responsible for facilitating the efflux of excessive intracellular drugs, thus giving rise to a significant impairment of chemotherapeutic effects [134,135]. The ABC transporter families play major roles in chemoresistance arising in CRC, due to their overexpression [18,20,21]. For instance, overexpression of the ABCB1 efflux transporter gave rise to 5-FU resistance in CRC cell lines [136], while most of the ABC transporters are responsible for DOX resistance [16].…”

Section: Drug Resistance In Crcmentioning

confidence: 99%

“…Several studies have been conducted to identify the mechanisms of chemoresistance and in turn find solutions to overcome this fundamental problem. Chemoresistance in CRC has shown to generally arises due to different mechanisms, such as ATP-binding cassette (ABC) transporters, different signalling pathways (Wnt/βcatenin, Phosphatidylinositol-4,5-bisphosphate 3-kinase/Protein Kinase B (PI3K/AKT), Epithelial Growth Factor Receptor-Rat Sarcoma-Mitogen Activated Protein Kinase (EGFR-RAS-MAPK), Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor (VEGF/VEGFR) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)), apoptosis, autophagy, cell cycle control, specific drug targets, DNA damage repair, epithelial mesenchymal transition (EMT) and drug metabolism [12,[17][18][19][20][21]. Despite the identification of all these mechanisms, the precise mechanisms causing CRC chemoresistance remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, alterations in ncRNA expression have shown to also be involved in regulating several protein targets or molecular pathways which eventually lead to or inhibit drug resistance [22]. Among the different ncRNAs identified to date, microRNAs (miRNAs) and long ncRNA (lncRNAs) are the two most studied ncRNAs involved in CRC chemoresistance, with circular RNAs (circRNAs) also gaining interest lately [20,[23][24][25][26][27]. This review article will focus on highlighting and summarising some of the recently identified/validated key molecular players from three ncRNA families; mainly miRNAs, lncRNAs and circRNAs and the molecular mechanisms by which these ncRNAs affect CRC chemoresistance and sensitivity for the drugs 5-FU, OXA, Cisplatin and DOX.…”

Section: Introductionmentioning

confidence: 99%

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The Mechanistic Roles of ncRNAs in Promoting and Supporting Chemoresistance of Colorectal Cancer

Micallef

Baron

2021

ncRNA

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Colorectal Cancer (CRC) is one of the most common gastrointestinal malignancies which has quite a high mortality rate. Despite the advances made in CRC treatment, effective therapy is still quite challenging, particularly due to resistance arising throughout the treatment regimen. Several studies have been carried out to identify CRC chemoresistance mechanisms, with research showing different signalling pathways, certain ATP binding cassette (ABC) transporters and epithelial mesenchymal transition (EMT), among others to be responsible for the failure of CRC chemotherapies. In the last decade, it has become increasingly evident that certain non-coding RNA (ncRNA) families are involved in chemoresistance. Research investigations have demonstrated that dysregulation of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) contribute towards promoting resistance in CRC via different mechanisms. Considering the currently available data on this phenomenon, a better understanding of how these ncRNAs participate in chemoresistance can lead to suitable solutions to overcome this problem in CRC. This review will first focus on discussing the different mechanisms of CRC resistance identified so far. The focus will then shift onto the roles of miRNAs, lncRNAs and circRNAs in promoting 5-fluorouracil (5-FU), oxaliplatin (OXA), cisplatin and doxorubicin (DOX) resistance in CRC, specifically using ncRNAs which have been recently identified and validated under in vivo or in vitro conditions.

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Section: Drug Resistance In Crcmentioning

confidence: 99%

Section: Drug Resistance In Crcmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Mechanistic Roles of ncRNAs in Promoting and Supporting Chemoresistance of Colorectal Cancer

Micallef

Baron

2021

ncRNA

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“…Treatment failure is related to the known low selectivity of drugs against tumor cells, their side effects, and the generation of drug resistance mediated by several mechanisms. Therefore, novel approaches are required to develop therapeutic alternatives that can improve cancer treatment or enhance the antitumor effects of existing chemotherapeutic agents [38,39]. In this context, numerous natural chemotherapeutic or chemopreventive agents have been isolated and are currently being used for cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Antitumor Effect of the Ethanolic Extract from Seeds of Euphorbia lathyris in Colorectal Cancer

et al. 2021

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The seeds of Euphorbia lathyris have been used in traditional medicine to treat various medical conditions. However, neither all of their active biocompounds nor the molecular mechanisms underlying their therapeutic effects have been described. A new ethanolic extract of defatted flour from mature seeds of Euphorbia lathyris showed a high total polyphenol content and significant antioxidant activity. Chromatographic analysis showed that esculetin, euphorbetin, gaultherin, and kaempferol-3-rutinoside were the most abundant polyphenolic bioactive compounds. Antiproliferative assays showed a high and selective antitumor activity against colon cancer cell lines (T84 and HCT-15). In addition, a significant antiproliferative activity against glioblastoma multiforme cells was also demonstrated. Its mechanism of action to induce cell death was mediated by the overexpression of caspases 9, 3, and 8, and by activation of autophagy. Interestingly, a reduction in the migration capacity of colon cancer cells and a significant antiangiogenic effect on human umbilical vein endothelial cells were also demonstrated. Finally, the extract significantly reduced the subpopulations of cancer stem cells. This extract could be the basis to develop new therapeutic strategies for the treatment of colon cancer, although further experiments will be necessary to determine its in vivo effects.

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Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatment

Franz,

Jötten,

Wührl

et al. 2023

Cancer Reports

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BackgroundColorectal cancer ranks second in terms of cancer associated deaths worldwide, whereas miRNA play a pivotal role in the etiology of cancer and its metastases.AimsStudying the expression and cellular function of miR‐18a in metastatic colorectal cancer and association to progression‐free survival.Methods and ResultsColorectal liver metastases (N = 123) and primary colorectal cancer (N = 27) where analyzed by RT‐PCR and correlated with clinical follow up data. Invasion and migration assays were performed with the liver metastatic cell line LIM2099 after miR‐18a knockdown. Cell viability under FOLFOX treatment and knockdown was measured. We found that the expression of miR‐18a was increased 4.38‐fold in liver metastases and 3.86‐fold in colorectal tumor tissue compared to healthy liver tissue and colorectal mucosa, respectively (p ≤ .001). Patients with a high miR‐18a expression in liver metastases had a progression‐free survival (PFS) of 13.6 months versus 8.9 months in patients with low expression (N = 123; p = .024). In vitro migration of LIM2099 cells was reduced after miR‐18a knockdown and cell viability was significantly increased after miR‐18a knockdown and treatment with folinic acid or oxaliplatin. Subgroup analysis of PFS revealed significant benefits for patients with high miR‐18a expression receiving 5‐FU, folinic acid or oxaliplatin.ConclusionsHigh expression of miR‐18a in colorectal liver metastases might have a protective effect after resection of metastases and FOLFOX treatment regarding PFS.

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MicroRNAs and colorectal cancer chemoresistance: New solution for old problem

Cited by 49 publications

References 149 publications

The Mechanistic Roles of ncRNAs in Promoting and Supporting Chemoresistance of Colorectal Cancer

The Mechanistic Roles of ncRNAs in Promoting and Supporting Chemoresistance of Colorectal Cancer

Antitumor Effect of the Ethanolic Extract from Seeds of Euphorbia lathyris in Colorectal Cancer

Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatment

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