• Exosome
• Gastroenterological cancer
• MicroRNA
• Saliva
• Serum
• Urine
• miR

• esophageal squamous cell carcinoma
• microRNA-106b
• microRNA-1246
• serum

• Steroid-induced osteonecrosis of the femoral head (SONFH)
• biomarkers
• hsa-miR-135b-5p
• serum exosomal miRNAs

• Chemoresistance
• Colorectal cancer
• Exosome
• MicroRNAs

• Notch1
• breast cancer
• invasion
• microRNA-34a
• proliferation

Lung cancer is a leading cause of cancer mortality worldwide. In tumors, the important role of noncoding RNA regulatory networks has been more and more reveal. EGFR has been identified as an oncogenic driver of NSCLC, especially activating mutations EGFR and its inhibition with specific TKIs can generate dramatic tumor responses. Studies have shown that EGFR plays significant roles in the progression of NSCLC. Subset analysis of the small proportion of patients with EGFR-mutant lung cancer showed a disease-free survival benefit, but was underpowered to detect a survival advantage. Herein, we highlight the progression of EGFR, noncoding RNA, and their roles in carcinogenesis. We also focus on anti-lung cancer drug development and EGFR-related drug resistance.

• epidermal growth factor receptor (EGFR)
• lung cancer
• noncoding RNA
• precision medicine

• Delta-like 1
• Molecular target
• Neuroblastoma
• Notch pathway
• miRNAs

• Hepatocellular carcinoma
• Refractoriness
• Transcatheter arterial chemoembolization
• c-Met

• Circulation
• Colorectal cancer
• Diagnosis
• MicroRNA
• Prediction
• Prognosis

Lung cancer is a leading cause of cancer mortality worldwide. Several molecular pathways underlying mechanisms of this disease have been partly elucidated, among which the epidermal growth factor receptor (EGFR) pathway is one of the well-known signaling cascades that plays a critical role in tumorigenesis. Dysregulation of the EGFR signaling is frequently found in lung cancer. The strategies to effectively inhibit EGFR signaling pathway have been mounted for developing anticancer therapeutic agents. However, most anti-EGFR-targeted agents fail to repress cancer progression because of developing drug-resistance. Therefore, studies of the mechanisms underpinning the resistance toward anti-EGFR agents may provide important findings for lung cancer treatment using anti-EGFR therapies. Recently, increasing numbers of miRNAs are correlated with the drug resistance of lung cancer cells to anti-EGFR agents, indicating that miRNAs may serve as novel targets and/or promising predictive biomarkers for anti-EGFR therapy. In this paper, we summarize the emerging role of miRNAs as regulators to modulate the EGFR signaling and the resistance of lung cancer cells to anti-EGFR therapy. We also highlight the evidence supporting the use of miRNAs as biomarkers for response to anti-EGFR agents and as novel therapeutic targets to circumvent the resistance of lung cancer cells to EGFR inhibitors.

Functional microRNAs (miRNAs) in exosomes have been recognised as potential stable biomarkers in cancers. The aim of this study is to identify specific miRNAs in exosome as serum biomarkers for the early detection of recurrence in human colorectal cancer (CRC).

Serum samples were sequentially obtained from six patients with and without recurrent CRC. The miRNAs were purified from exosomes, and miRNA microarray analysis was performed. The miRNA expression profiles and copy number aberrations were explored using microarray and array CGH analyses in 124 CRC tissues. Then, we validated exosomal miRNAs in 2 serum sample sets (90 and 209 CRC patients) by quantitative real-time RT–PCR.

Exosomal miR-17-92a cluster expression level in serum was correlated with the recurrence of CRC. Exosomal miR-19a expression levels in serum were significantly increased in patients with CRC as compared with healthy individuals with gene amplification. The CRC patients with high exosomal miR-19a expression showed poorer prognoses than the low expression group (P<0.001).

Abundant expression of exosomal miR-19a in serum was identified as a prognostic biomarker for recurrence in CRC patients.

• bone marrow
• disseminated tumor cells
• hepatocellular carcinoma
• miR-615-3p
• microRNA

MicroRNA-200c (miR-200c) is one of the short noncoding RNAs that play crucial roles in tumorigenesis and tumor progression. It also acts as considerable modulator in the process of epithelial-to-mesenchymal transition (EMT), a cell development regulating process that affects tumor development and metastasis. However, the role of miR-200c in bladder cancer cells and its mechanism has not been well studied. The purpose of this study was to determine the potential role of miR-200c in regulating EMT and how it contributed to bladder cancer cells in invasion, migration and proliferation.

Real-time reverse transcription-PCR was used to identify and validate the differential expression of MiR-200c involved in EMT in 4 bladder cancer cell lines and clinical specimens. A list of potential miR-200 direct targets was identified through the TargetScan database. The precursor of miR-200c was over-expressed in UMUC-3 and T24 cells using a lentivirus construct, respectively. Protein expression and signaling pathway modulation were validated through Western blot analysis and confocal microscopy, whereas BMI-1 and E2F3, direct target of miR-200c, were validated by using the wild-type and mutant 3′-untranslated region BMI-1/E2F3 luciferase reporters.

We demonstrate that MiR-200c is down-regulated in bladder cancer specimens compared with adjacent ones in the same patient. Luciferase assays showed that the direct down-regulation of BMI-1 and E2F3 were miR-200c-dependent because mutations in the two putative miR-200c-binding sites have rescued the inhibitory effect. Over-expression of miR-200c in bladder cancer cells resulted in significantly decreased the capacities of cell invasion, migration and proliferation. miR-200c over-expression resulted in conspicuous down-regulation of BMI-1and E2F3 expression and in a concomitant increase in E-cadherin levels.

miR-200c appears to control the EMT process through BMI-1 in bladder cancer cells, and it inhibits their proliferation through down-regulating E2F3. The targets of miR-200c include BMI-1 and E2F3, which are a novel regulator of EMT and a regulator of proliferation, respectively.

The online version of this article (doi:10.1186/s12967-014-0305-z) contains supplementary material, which is available to authorized users.

• Apoptosis/genetics
• Biomarkers, Tumor/biosynthesis
• Biomarkers, Tumor/genetics
• Carcinoma, Non-Small-Cell Lung/genetics
• Carcinoma, Non-Small-Cell Lung/pathology
• Cell Line, Tumor
• Cell Proliferation/genetics
• Forkhead Box Protein O3
• Forkhead Transcription Factors/biosynthesis
• Forkhead Transcription Factors/genetics
• Gene Expression Regulation, Neoplastic
• Humans
• Lymphatic Metastasis/pathology
• MicroRNAs/biosynthesis
• MicroRNAs/genetics
• Neoplasm Invasiveness/genetics

An improvement in pancreatic cancer treatment represents an urgent medical goal. Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchanged during the past decades. Increasing knowledge about the molecular pathogenesis of the disease has shown that genetic alterations, such as mutations of K-ras, and especially epigenetic dysregulation of tumor-associated genes, such as silencing of the tumor suppressor p16^ink4a, are hallmarks of pancreatic cancer. Here, we describe genes that are commonly affected by epigenetic dysregulation in pancreatic cancer via DNA methylation, histone acetylation or miRNA (microRNA) expression, and review the implications on pancreatic cancer biology such as epithelial-mesenchymal transition, morphological pattern formation, or cancer stem cell regulation during carcinogenesis from PanIN (pancreatic intraepithelial lesions) to invasive cancer and resistance development. Epigenetic drugs, such as DNA methyltransferases or histone deactylase inhibitors, have shown promising preclinical results in pancreatic cancer and are currently in early phases of clinical development. Combinations of epigenetic drugs with established cytotoxic drugs or targeted therapies are promising approaches to improve the poor response and survival rate of pancreatic cancer patients.

• Pancreatic cancer
• Epigenetics
• DNA methylation
• Histone modification
• microRNA
• Targeted therapy
• Epithelial-mesenchymal transition

• Animals
• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/genetics
• Drug Design
• Epigenesis, Genetic/drug effects
• Gene Expression Regulation, Neoplastic
• Genetic Predisposition to Disease
• Humans
• Molecular Targeted Therapy
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/physiopathology
• Phenotype
• Treatment Outcome

• cdk2
• growth inhibition
• microrna
• mir-509-3p
• pik3c2a
• rac1

• Cell Cycle/genetics
• Cell Movement/genetics
• Cell Proliferation/genetics
• Cyclin-Dependent Kinase 2/genetics
• Cyclin-Dependent Kinase 2/metabolism
• Down-Regulation/genetics
• HeLa Cells
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Microarray Analysis
• Neoplasms/genetics
• Neoplasms/therapy
• Neoplastic Stem Cells
• Phosphatidylinositol 3-Kinases/genetics
• Phosphatidylinositol 3-Kinases/metabolism
• RNA, Small Interfering/genetics
• Transgenes/genetics
• rac1 GTP-Binding Protein/genetics
• rac1 GTP-Binding Protein/metabolism

MicroRNAs (miRNAs) have been documented as playing important roles in cancer development. In this study, we investigated the role of miR-124 in breast cancer and clarified the regulation of flotillin-1 (FLOT1) by miR-124.

The expression levels of miR-124 were examined in breast cancer cell lines and patient specimens using quantitative reverse transcription-PCR. The clinicopathological significance of the resultant data was later analyzed. Next, we explored the function of miR-124 to determine its potential roles on cancer cell growth and migration in vitro. A luciferase reporter assay was conducted to confirm the target gene of miR-124, and the results were validated in cell lines and patient specimens.

We found that miR-124 expression was significantly downregulated in breast cancer cell lines and patient specimen compared with normal cell lines and paired adjacent normal tissues (P < 0.0001), respectively. MiR-124 was also associated with tumor node metastasis (TNM) stage (P = 0.0007) and lymph node metastasis (P = 0.0004). In breast cancer cell lines, the ectopic expression of miR-124 inhibited cell growth and migration in vitro. Moreover, we identified the FLOT1 gene as a novel direct target of miR-124, and miR-124 ectopic expression significantly inhibited FLOT1. Luciferase assays confirmed that miR-124 could directly bind to the 3′ untranslated region of FLOT1 and suppress translation. Moreover, FLOT1 was widely upregulated, and inversely correlated with miR-124 in breast cancer tissues. Consistent with the effect of miR-124, the knockdown of FLOT1 significantly inhibited breast cancer cell growth and migration. We also observed that the rescue expression of FLOT1 partially restored the effects of miR-124.

Our study demonstrated that miR-124 might be a tumor suppressor in breast cancer via the regulation of FLOT1. This microRNA could serve as a potential diagnostic marker and therapeutic target for breast cancer.

Autophagy represents a cell’s response to stress. It is an evolutionarily conserved process with diversified roles. Indeed, it controls intracellular homeostasis by degradation and/or recycling intracellular metabolic material, supplies energy, provides nutrients, eliminates cytotoxic materials and damaged proteins and organelles. Moreover, autophagy is involved in several diseases. Recent evidences support a relationship between several classes of nanomaterials and autophagy perturbation, both induction and blockade, in many biological models. In fact, the autophagic mechanism represents a common cellular response to nanomaterials. On the other hand, the dynamic nature of autophagy in cancer biology is an intriguing approach for cancer therapeutics, since during tumour development and therapy, autophagy has been reported to trigger both an early cell survival and a late cell death. The use of nanomaterials in cancer treatment to deliver chemotherapeutic drugs and target tumours is well known. Recently, autophagy modulation mediated by nanomaterials has become an appealing notion in nanomedicine therapeutics, since it can be exploited as adjuvant in chemotherapy or in the development of cancer vaccines or as a potential anti-cancer agent. Herein, we summarize the effects of nanomaterials on autophagic processes in cancer, also considering the therapeutic outcome of synergism between nanomaterials and autophagy to improve existing cancer therapies.