Role of microRNA in anticancer drug resistance
TL;DR: Accumulating evidence is revealing an important role of miRNAs in anticancer drug resistance and miRNA expression profiling can be correlated with the development of antic cancer drug resistance.
Abstract: Chemotherapy has been widely used in treatment of cancer, both as systemic therapy and as part of local treatment. Unfortunately, many kinds of cancer are still refractory to chemotherapy. The anticancer drug resistance mechanisms have been extensively explored, yet have not been fully characterized. Recent works have underlined the involvement of noncoding RNAs in cancer development, with several studies regarding their possible involvement in the evolution of drug resistance. MicroRNAs (miRNAs) are endogenous small noncoding RNAs (20-23 nucleotides) that negatively regulate the gene expressions at the post-transcriptional level by base pairing to the 3' untranslated region of target messenger RNAs. Evidence is emerging that particular microRNAs (miRNA) alterations are involved in the initiation and progression of human cancer. More recently, accumulating evidence is revealing an important role of miRNAs in anticancer drug resistance and miRNA expression profiling can be correlated with the development of anticancer drug resistance. The micro-RNA-mediated form of drug resistance adds yet another mechanism of drug resistance. So, exploiting the emerging knowledge of miRNAs for the development of new human therapeutic applications for overcoming anticancer drug resistance will be important.
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TL;DR: The findings suggest that miR‐181b could play a role in the development of MDR in both gastric and lung cancer cell lines, at least in part, by modulation of apoptosis via targeting BCL2.
Abstract: MicroRNAs (miRNAs) are short noncoding RNA molecules, which posttranscriptionally regulate genes expression and play crucial roles in diverse biological processes, such as development, differentiation, apoptosis and proliferation. Here, we investigated the possible role of miRNAs in the development of multidrug resistance (MDR) in human gastric and lung cancer cell lines. We found that miR-181b was downregulated in both multidrug-resistant human gastric cancer cell line SGC7901/vincristine (VCR) and multidrug-resistant human lung cancer cell line A549/cisplatin (CDDP), and the downregulation of miR-181b in SGC7901/VCR and A549/CDDP cells was concurrent with the upregulation of BCL2 protein, compared with the parental SGC7901 and A549 cell lines, respectively. In vitro drug sensitivity assay demonstrated that overexpression of miR-181b sensitized SGC7901/VCR and A549/CDDP cells to anticancer drugs, respectively. The luciferase activity of a BCL2 3'-untranslated region-based reporter construct in SGC7901/VCR and A549/CDDP cells suggests that a new target site in the 3'UTR of BCL2 of the mature miR-181s (miR-181a, miR-181b, miR-181c and miR-181d) was found. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively. Taken together, our findings suggest that miR-181b could play a role in the development of MDR in both gastric and lung cancer cell lines, at least in part, by modulation of apoptosis via targeting BCL2.
281 citations
TL;DR: New perspectives for enhancing the efficacy of gemcitabine are outlined after reviewing the related factors of gem citabine metabolism, mechanism of action, and chemoresistance.
Abstract: Pancreatic ductal adenocarcinoma (PDAC), generally known as pancreatic cancer (PC), ranks the fourth leading cause of cancer-related deaths in the western world. While the incidence of pancreatic cancer is displaying a rising tendency every year, the mortality rate has not decreased significantly because of late diagnosis, early metastasis, and limited reaction to chemotherapy or radiotherapy. Adjuvant chemotherapy after surgical resection is typically the preferred option to treat early pancreatic cancer. Although 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel can profoundly improve the prognosis of advanced pancreatic cancer, the development of chemoresistance still leads to poor clinical outcomes. Chemoresistance is multifactorial as a result of the interaction among pancreatic cancer cells, cancer stem cells, and the tumor microenvironment. Nevertheless, more pancreatic cancer patients will benefit from precision treatment and targeted drugs. Therefore, we outline new perspectives for enhancing the efficacy of gemcitabine after reviewing the related factors of gemcitabine metabolism, mechanism of action, and chemoresistance.
271 citations
Cites background from "Role of microRNA in anticancer drug..."
...The consequences of miRNA binding are that the bound mRNA is either silenced or degraded, resulting in reduced levels of the protein encoded by the mRNA [82]....
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TL;DR: The current knowledge in this area is reviewed, including evidence of miRNA involvement in cancer drug resistance, and many pro-apoptotic miRNAs target anti-APoptotic mRNAs or their positive regulators.
253 citations
TL;DR: Emerging results suggest that specific targeting of miRNAs by different approaches could open new avenues for cancer treatment through overcoming drug resistance and thereby improve the outcome of cancer therapy.
207 citations
Cites background from "Role of microRNA in anticancer drug..."
...Experimental evidence also revealed thatmiRNAs regulate anti-cancer drug resistance (Zheng et al., 2010), suggesting that targeting specific miRNAs could be a novel therapeutic approach for the treatment of cancers by increasing the drug sensitivity of...
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TL;DR: The findings suggest that miR-200bc/429 cluster could play a role in the development of MDR in both gastric and lung cancer cell lines, at least in part by modulation of apoptosis via targeting BCL2 and XIAP.
Abstract: Purpose
MicroRNAs (miRNAs) are short non-coding RNA molecules, which post-transcriptionally regulate genes expression and play crucial roles in diverse biological processes. Recent studies have shown that dysregulation of miRNAs might modulate the resistance of cancer cells to anti-cancer drugs, yet the modulation mechanism is not fully understood. We aimed to investigate the possible role of miRNAs in the development of multidrug resistance (MDR) in human gastric and lung cancer cell lines.
177 citations
References
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TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
32,946 citations
TL;DR: A new, bead-based flow cytometric miRNA expression profiling method is used to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers, and finds the miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours.
Abstract: Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.
9,470 citations
"Role of microRNA in anticancer drug..." refers background or result in this paper
...Indeed, in certain cases miRNA profiles provide more accurate prognostication than mRNAbased disease signatures, which have been shown to correlate and define cancer subtypes.(15) We believe that miRNA expression analysis could be an effective tool to predict the thera-...
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...of miRNAs has been applied to clinical samples and successfully distinguishes cancers from normal organ, and indeed is better at classifying poorly differentiated tumors than previous mRNA expression profiling.(15,73) For instance, the PTEN Figure 2....
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...Aberrant levels of microRNA (miRNA) have been reported in a variety of human cancers.(13,15) They have been shown to have both diagnostic and prognostic significance and to constitute a novel target for cancer treatment....
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TL;DR: MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment and has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.
Abstract: MicroRNA (miRNA ) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein- coding genes involved in cancer.
6,345 citations
"Role of microRNA in anticancer drug..." refers background in this paper
...As the name implies, miRNAs are small RNAs usually 19–23 bp in length or shorter, which are produced in all mammalian cells.(12,13) Lacking the ability to encode a protein, these single-stranded miRNAs bind mainly to the 30 UTR of protein encoding mRNAs through sequences that are imper-...
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...Aberrant levels of microRNA (miRNA) have been reported in a variety of human cancers.(13,15) They have been shown to have both diagnostic and prognostic significance and to constitute a novel target for cancer treatment....
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Journal Article•
TL;DR: The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery as discussed by the authors.
Abstract: MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein- coding genes involved in cancer.
6,306 citations
TL;DR: In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival.
Abstract: Background A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer. Methods We randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival. Results ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer. Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group (46 percent and 45 percent, respectively), as were the numbers of deaths within 30 days after surgery. The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group. With a median follow-up of four years, 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died. As compared with the surgery group, the perioperative-chemotherapy group had a higher likelihood of overall survival (hazard ratio for death, 0.75; 95 percent confidence interval, 0.60 to 0.93; P = 0.009; five-year survival rate, 36 percent vs. 23 percent) and of progression-free survival (hazard ratio for progression, 0.66; 95 percent confidence interval, 0.53 to 0.81; P<0.001). Conclusions In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival. (Current Controlled Trials number, ISRCTN93793971.)
5,133 citations
"Role of microRNA in anticancer drug..." refers background in this paper
...Chemotherapy remains the primary treatment for both resectable and advanced gastric cancer as to improving overall survival and quality of life for patients.(47,48) In many cases, however, therapies fail because of multidrug resistance (MDR) of cancer cells either intrinsic or acquired after an initial round of treatment....
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