Jiaojiao Ma

Function of miRNA in controlling drug resistance of human cancers.

Drug resistance is a major obstacle to successful cancer treatment. The identification of new approaches that can circumvent this problem will lead to improved clinical strategies and outcomes for cancer patients. MicroRNAs, key post-transcriptional gene regulators, are known to be master regulators of many cellular processes, including drug resistance. Drug resistance related microRNAs can be used to stratify patients and select those treatment options most likely to prove efficacious for a particular individual. This review summarizes the recent advances in drug resistance related microRNAs in cancer, and also analyzes the clinical and therapeutic applications they provide. We also envisage future developments toward the potential applications of these microRNAs to cancer treatment. In the future, more investigations should be performed to promote the success of therapeutic-clinical use of microRNAs in cancer.

Epigenetic Regulation of microRNAs in Gastric Cancer

Gastric cancer is one of the most common cancers and accounts for a large proportion of cancer-related deaths in the world, while the pathogenesis of it is still not clear. Epigenetic changes have been found to participate in the development and progression of gastric cancer. Epigenetic changes involve methylation of cytosines in DNA, modifications of histone, chromatin remodeling, and alterations in the expression of microRNAs. MicroRNAs, a family of small non-coding RNAs, have been demonstrated to participate in many fundamental biological processes including the carcinogenesis of gastric cancer. Previous studies have shown that the downregulation of microRNAs are often caused by the methylation in the CpG islands of microRNA promoters. Here, we have summarized the functions and molecular mechanisms of gastric cancer related methylated microRNAs in gastric carcinogenesis. We further envisage the clinical application of microRNA methylation in the early diagnosis, treatment and prognosis assessment of gastric cancer.

Targeted therapy in esophageal cancer

ABSTRACT An increasing number of patients are diagnosed with esophageal cancer at an advanced stages, and only a small group of them can benefit from the traditional chemotherapy and radiotherapy. So far, multiple monoclonal antibodies and tyrosine kinase inhibitors have been developed, alone or in combination with traditional therapy, to improve the prognosis of patients with advanced esophageal cancer. This review summarizes the recent advances of targeted therapies against EGFR, HER2, VEGFR and c-MET in esophageal cancer. More clinical trials should be performed to evaluate the efficacy and safety of various targeted therapy regimens. Future basic research should focus on investigating the molecular mechanisms of therapeutic targets in esophageal cancer.

Role of MiRNAs in Inflammatory Bowel Disease

Inflammatory bowel diseases (IBD), mainly including Crohn’s disease and ulcerative colitis, are characterized by chronic inflammation of the gastrointestinal tract. Despite improvements in detection, drug treatment and surgery, the pathogenesis of IBD has not been clarified. A number of miRNAs have been found to be involved in the initiation, development and progression of IBD, and they may have the potential to be used as biomarkers and therapeutic targets. Here, we have summarized the recent advances about the roles of miRNAs in IBD and analyzed the contribution of miRNAs to general diagnosis, differential diagnosis and activity judgment of IBD. Furthermore, we have also elaborated the promising role of miRNAs in IBD-related cancer prevention and prognosis prediction.

Role of miR-483 in digestive tract cancers: from basic research to clinical value

Digestive tract cancers (DTCs) is the most common malignant tumors in the world. Despite surgery and medical technology have witnessed the increasing development and sharp advancement in the past decade, DTCs remain a critical concern with high morbidity and mortality. Since a class of small noncoding RNAs termed miRNAs were identified several years ago, increasing studies have attempted to illustrate the relationship between the specific miRNAs dysregulated expression levels and the diseases phenotypic changes. For example, microRNA-483 (miR-483) aberrant expression plays a pivotal part in tumor biology in a variety of human cancer, including DTCs. In this review, we focus on the present key findings from recent profiling studies, discuss the use of miR-483 as a novel biomarker for DTCs. At the same time, we emphasize the significant diversities and technical difficulties must be overcome before clinically relevant signatures arose. It is believed that this might provide researchers an insight into the molecular targeting cancer treatment.

Biological implications and clinical value of mir-210 in gastrointestinal cancer

ABSTRACT Introduction: Hypoxia, a common feature of tumor microenvironment, is known to accelerate tumor development and growth by promoting the formation of a neoplastic environment. Recent studies have provided a wealth of evidence that miRNAs are significant members of the adaptive response to low oxygen in tumors. miR-210 is one of the hypoxia-induced miRNAs, which has been reported extensively in cancer researches. However, there is no systematic discussion about the role of miR-210 in gastrointestinal cancer. We conducted a literature research in database including PubMed, Elsevier Science Direct and Medline before 16 September 2016, in order to collect articles of miR-210 in gastrointestinal cancer. Areas covered: In the present review, we mainly discuss the following aspects: hypoxia-induced dysregulation of miR-210, the expression of miR-210 and tumorigenesis, the resultant changes of miR-210 targets and its roles in different types of gastrointestinal cancer progression, the diagnostic, therapeutic and prognostic value of miR-210 in gastrointestinal cancer. Expert commentary: Numerous researches have demonstrated the values of miR-210 in cancer diagnosis, prognosis and targeted therapies, especially in gastrointestinal cancers. However, there are also some existing problems and challenges in translating the new research findings into clinical utility. Further investigations and studies are still urgently required.

The role of cell-free DNA in predicting colorectal cancer prognosis

ABSTRACT Introduction: Colorectal cancer is a cancer of the digestive system with poor prognosis. Cell-free DNA has received much attention with its unique predominance, especially in colorectal cancer. Areas covered: This study has summarized recent advancements and challenges regarding cell-free DNA in predicting CRC prognosis. Furthermore, the authors make predictions on the potential developments concerning cell-free DNA in future prognosis prediction techniques. Expert commentary: Cell-free DNA has the value of predicting CRC prognosis as an important biomarke. Further clinical trials should be performed to promote translating cell-free DNA into clinical applications.

Reciprocal regulations between miRNAs and HIF-1α in human cancers

Hypoxia inducible factor-1α (HIF-1α) is a central molecule involved in mediating cellular processes. Alterations of HIF-1α and hypoxically regulated microRNAs (miRNAs) are correlated with patients’ outcome in various cancers, indicating their crucial roles on cancer development. Recently, an increasing number of studies have revealed the intricate regulations between miRNAs and HIF-1α in modulating a wide variety of processes, including proliferation, metastasis, apoptosis, and drug resistance, etc. miRNAs are a class of small noncoding RNAs which function as negative regulators by directly targeting mRNAs. Evidence shows that miRNAs can be regulated by HIF-1α at transcriptional level. In turn, HIF-1α itself can be modulated by many miRNAs whose alterations have been implicated in tumorigenesis, thus forming a reciprocal regulation network. These findings add a new layer of complexity to our understanding of HIF-1α regulatory networks. Here, we will provide a comprehensive overview of the current advances about the bidirectional interactions between HIF-1α and miRNAs in human cancers. Besides, the review will summarize the roles of miRNAs/HIF-1α crosstalk according to various cellular processes. Finally, the potential values of miRNAs/HIF-1α loops in clinical applications are discussed.

Molecular mechanisms and clinical implications of miRNAs in drug resistance of esophageal cancer

ABSTRACT Introduction: With the increasing incidence of esophageal cancer, drug resistance is becoming a major obstacle to successful cancer therapy since chemotherapy is regarded as a curative approach to inhibit cancer cell proliferation. Despite the great progress in anticancer treatment achieved during the last decades, the mechanisms of multidrug resistance have not been completely elucidated. Recently, accumulating studies and pre-clinical reports highlighted the role of miRNAs in the drug resistance of esophageal cancer. Areas covered: In this review, we mainly summarized the current advances of miRNAs in esophageal cancer and the mechanisms underlying drug resistance. We also reviewed the potential role of miRNAs as biomarkers for predicting drug response and prognosis. Finally, we envisaged the future orientation and challenges in translating the existing knowledge of drug resistance related miRNAs into clinical applications. Expert commentary: Based on the current knowledge of certain miRNAs, we believe that miRNAs would be helpful to overcome the drug resistance and provide personalized treatment for patients with esophageal cancer. The aims of this study were to provide a comprehensive summary on the emerging role of miRNAs in the drug resistance of esophageal cancer and attract broad attention of more researchers on this field.

Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer

ABSTRACT Introduction: Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer. Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications. Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.