Plasma microRNA profiles: identification of <i>miR-23a</i> as a novel biomarker for chemoresistance in esophageal squamous cell carcinoma

Komatsu, Shuhei; Ichikawa, Daisuke; Kawaguchi, Tsutomu; Takeshita, Hitoshi; Miyamae, Mahito; Ohashi, Takuma; Okajima, Wataru; Imamura, Taisuke; Kiuchi, Jun; Arita, Tomohiro; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Okamoto, Kazuma; Otsuji, Eigo

doi:10.18632/oncotarget.11500

Cited by 49 publications

(58 citation statements)

References 76 publications

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“…miRNA-152 and miRNA-185 were demonstrated to be significantly downregulated in SKOV3/DDP and A2780/DDP cells (14). Previous studies have demonstrated that miRNA-21 is involved in drug resistance in multiple types of cancer, including gastric, breast and lung cancer, via regulation of PTEN (7,8,15). In the present study, the expression level of miRNA-21 in SKOV3/DDP cells was significantly higher than in SKOV3 cells, as detected by qPCR.…”

Section: Discussionsupporting

confidence: 52%

“…Multiple previous reports have indicated that dysregulation of miRNA target genes promotes drug resistance, and inhibition of miRNAs may reverse drug resistance (2,3). miRNA-21 is overexpressed in multiple types of cancer, and promotes the initiation of cancer, progression and drug-resistance (4)(5)(6)(7)(8)(9). miRNA-21 impacts tumorigenesis by negatively regulating several targets.…”

Section: Introductionmentioning

confidence: 99%

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miRNA-21 enhances chemoresistance to cisplatin in epithelial ovarian cancer by negatively regulating PTEN

Chen

Tian

et al. 2017

Oncology Letters

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Abstract. MicroRNAs (miRNAs) are small non-coding RNAs, 8-23 nucleotides in length, which regulate gene expression at the post-transcriptional level. The present study was performed to analyze the association between microRNA-21 and cisplatin resistance in epithelial ovarian cancer (EOC) SKOV3 and SKOV3/DDP cells. In this experiment, the resistance of SKOV3 and SKOV3/DDP cells to cisplatin was evaluated using the MTT assay. Reverse transcription-quantitative polymerase chain reaction analysis was used to assess miRNA-21 levels and phosphatase and tensin homolog (PTEN) mRNA levels. Western blotting was used to assess PTEN protein levels. miRNA-21 mimics or inhibitors were transfected into SKOV3 and SKOV3/DDP cells. Prior to transfection, higher expression levels of miRNA-21 were observed in SKOV3/DDP cells compared with SKOV3 cells. Following transfection with miRNA-21 mimics, SKOV3 cells demonstrated increased sensitivity to cisplatin compared with negative control cells. Following transfection with the miRNA-21 inhibitor, SKOV3/DDP cells demonstrated decreased sensitivity to cisplatin compared with negative control cells. Furthermore, PTEN mRNA expression levels in SKOV3 cells transfected with miRNA-21 mimics was significantly lower compared with negative control cells. These results suggested that miRNA-21 may regulate cisplatin resistance by negatively targeting PTEN in EOC. IntroductionEpithelial ovarian cancer (EOC) is one of the most common malignant gynecologic tumors. Debulking surgery followed by a combination of platinum and taxane based chemotherapy are widely used treatments for EOC at present. Although overall survival rates have increased slightly over the past 25 years, 5-year survival remains <50% (1). The high mortality rate of ovarian cancer is due to late-stage diagnosis and resistance to platinum-based chemotherapy. However, the mechanisms underlying cisplatin resistance in EOC remain to be fully understood.MicroRNAs (miRNAs) are small non-coding RNAs of 8-23 nucleotides that post-transcriptionally regulate gene expression. Multiple previous reports have indicated that dysregulation of miRNA target genes promotes drug resistance, and inhibition of miRNAs may reverse drug resistance (2,3). miRNA-21 is overexpressed in multiple types of cancer, and promotes the initiation of cancer, progression and drug-resistance (4-9). miRNA-21 impacts tumorigenesis by negatively regulating several targets. Phosphatase and tensin homolog (PTEN) is a tumor suppressor molecule. Inactivating mutations and deletions of the PTEN gene have been observed in multiple types of cancer. Notably, bioinformatics tools have demonstrated that the 3'-untranslated region of the PTEN gene harbors a putative binding site for miRNA-21 (10). miRNA-21 expression has been revealed to be markedly increased in ovarian cancer compared with benign ovarian tumor tissues (11). miRNA-21 expression was also demonstrated to be increased in drug-resistant ovarian cancer compared with drug-sensitive ovarian cancer serum. In the present study,...

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Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

miRNA-21 enhances chemoresistance to cisplatin in epithelial ovarian cancer by negatively regulating PTEN

Chen

Tian

et al. 2017

Oncology Letters

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“…Furthermore, some extracellular miRNAs occur not only through cell lysis but also through active secretion [25][26][27] and can function as intercellular transmitters 19,26,28,29 . Thus, various blood-based miRNAs have been identified, including those in this study, and can be used for cancer detection, monitoring tumor dynamics, and predicting prognosis and chemoresistance [30][31][32][33][34][35][36][37][38][39][40][41][42] . Recently, Kosaka and Ochiya et al suggested a novel mechanism -that miRNAs could facilitate the system of maintenance and surveillance against cancer progression.…”

mentioning

confidence: 99%

Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer

Imamura

Komatsu

Ichikawa

et al. 2017

Journal of the American College of Surgeons

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This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in pancreatic cancer (PCa) patients to clarify their potential as novel biomarkers and therapeutic targets. We used the microRNA array-based approach to select candidates by comparing plasma levels between PCa patients and healthy volunteers. Six down-regulated miRNAs (miR-107, miR-126, miR-451, miR-145, miR-491-5p, and miR-146b-5p) were selected. Small-and large-scale analyses using samples from 100 PCa patients and 80 healthy volunteers revealed that miR-107 was the most down-regulated miRNA in PCa patients compared with healthy volunteers (P < 0.0001; area under the receiver-operating characteristic curve, 0.851). A low miR-107 plasma level was significantly associated with advanced T stage, N stage, and liver metastasis and was an independent factor predicting poor prognosis in PCa patients (P = 0.0424; hazard ratio, 2.95). miR-107 overexpression in PCa cells induced G1/S arrest with the production of p21 and inhibited cell proliferation through the transcriptional regulation of Notch2. In vivo, the restoration and maintenance of the miR-107 plasma level significantly inhibited tumor progression in mice. Depletion of the tumor suppressor miR-107 in plasma relates to tumor progression and poor outcomes. The restoration of the plasma miR-107 level might be a novel anticancer treatment strategy for PCa.Pancreatic cancer (PCa) is the fourth leading cause of cancer-related death in Japan and the United States 1 and the seventh worldwide 2 . PCa is one of the most aggressive cancer types and constitutes a global health problem, with more than 330,000 cancer-related deaths annually 2 . Although perioperative chemo-and/or radiotherapy regimens, surgical techniques and perioperative management have greatly progressed, PCa continues to present an extremely poor prognosis. Even now, the median survival time of PCa patients is 5 to 8 months, and their 5-year survival rate is less than 10%. This is because PCa develops with no symptoms, local invasiveness, or metastases to distant organs in the early stage of its clinical course [3][4][5] . Therefore, novel early diagnostic tools and effective treatment strategies are urgently needed to improve the survival rate of PCa patients.Because understanding the molecular mechanisms of tumorigenesis and identifying clinical biomarkers and molecular targets for PCa contribute to improving the management of this lethal disease, several studies have attempted to detect the biological factors involved in the malignant potential of PCa 6, 7 . Nevertheless, in clinical settings, no molecule has been used as an early diagnostic biomarker, and only a few molecules have been

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“…As indicated by the usefulness of cell-free DNA and circulating tumor cells, the concept of "liquid biopsy" through circulating miRNAs may also provide ideal individualized therapeutic strategies for cancer patients and contribute to the development of precision medicine. Indeed, previous studies, including our own, have identified various blood-based miRNA biomarker candidates, which are useful for cancer detection, monitoring tumor dynamics, and predicting malignant potential, prognosis, and chemoresistance in cancer patients [32][33][34][35][36][37][38][39][40][41][42][43][44][45] .…”

Section: Circulating Micrornas Are a Promising Source Of Diagnostic Amentioning

confidence: 99%

Circulating microRNAs as a liquid biopsy: a next-generation clinical biomarker for diagnosis of gastric cancer

Komatsu¹,

Kiuchi²,

Imamura³

et al. 2018

JCMT

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Accumulating evidence has suggested the potential clinical utility of novel body fluid biomarkers, or "liquid biopsy", using circulating tumor cells and cell-free nucleic acids from cancer patients. Noninvasive and reproducible, liquid biopsy could provide the basis for individualized therapeutic strategies by identifying genetic and epigenetic aberrations that are closely associated with cancer initiation and progression. MicroRNAs (miRNAs) are short noncoding RNAs that posttranscriptionally regulate gene expression. They also play important roles in various physiological and developmental processes as oncogenic or tumor-suppressive regulators. Specific miRNA expression signatures have been identified in a number of human cancers. Circulating miRNAs have been detected in plasma and serum, and this in blood has attracted the attention of researchers for their potential as noninvasive biomarkers. Circulating miRNAs have emerged as tumorassociated biomarkers that reflect not only the existence of cancer, but also the dynamics, malignant potential, and drug resistance of tumors. Herein, we review the recent biological and clinical research on the circulating miRNAs of gastric cancer and discuss future perspectives for their clinical applications as a liquid biopsy.

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Plasma microRNA profiles: identification of miR-23a as a novel biomarker for chemoresistance in esophageal squamous cell carcinoma

Cited by 49 publications

References 76 publications

miRNA-21 enhances chemoresistance to cisplatin in epithelial ovarian cancer by negatively regulating PTEN

miRNA-21 enhances chemoresistance to cisplatin in epithelial ovarian cancer by negatively regulating PTEN

Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer

Circulating microRNAs as a liquid biopsy: a next-generation clinical biomarker for diagnosis of gastric cancer

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