• Cancer therapeutics
• Colorectal cancer
• Epithelial-mesenchymal transition
• Non-coding RNAs
• Signaling pathways

• Humans
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/metabolism
• Epithelial-Mesenchymal Transition/genetics
• RNA, Untranslated/genetics
• RNA, Untranslated/metabolism
• Neoplasm Metastasis
• Animals
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• RNA, Circular/genetics
• Drug Resistance, Neoplasm
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Signal Transduction

• CRISPR/Cas
• colorectal cancer
• colorectal cancer modeling
• gene therapy
• genome editing

• Humans
• CRISPR-Cas Systems
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/therapy
• Colorectal Neoplasms/diagnosis
• Gene Editing/methods
• Genetic Therapy/methods
• Animals
• Precision Medicine/methods
• Molecular Targeted Therapy

• ALKBH5
• Epithelial ovarian cancer
• Epithelial-mesenchymal transition
• Follicle-stimulating hormone
• Snail

• Humans
• Animals
• Female
• Mice
• Cell Line, Tumor
• Ovarian Neoplasms/drug therapy
• Follicle Stimulating Hormone/metabolism
• Epithelial-Mesenchymal Transition/genetics
• Demethylation
• AlkB Homolog 5, RNA Demethylase/metabolism
• Adenine/analogs & derivatives

• drug development

• Humans
• Transcription Factors/genetics
• Gene Expression Regulation/genetics
• Signal Transduction/genetics
• Neoplasms/drug therapy
• Neoplasms/genetics

• Cancer
• Invasion
• Metastasis
• MiR-150
• Migration

• Biomarker
• Colorectal cancer
• Exosome
• Metastasis
• miRNA

• AKT
• EMT
• MST4
• apoptosis
• breast cancer

• Female
• Humans
• Breast Neoplasms/drug therapy
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Epithelial-Mesenchymal Transition/genetics
• Lymphatic Metastasis
• Oncogenes
• Proto-Oncogene Proteins c-akt/metabolism
• Signal Transduction
• Protein Serine-Threonine Kinases/genetics

• artificial intelligence
• metastatic colorectal cancer
• ncRNA
• predictive biomarkers
• prognostic biomarkers

Epithelial-mesenchymal transition (EMT) is a fundamental process for embryonic development during which epithelial cells acquire mesenchymal characteristics, and the underlying mechanisms confer malignant features to carcinoma cells such as dissemination throughout the organism and resistance to anticancer treatments. During the past decades, an entire class of molecules, called non-coding RNA (ncRNA), has been characterized as a key regulator of almost every cellular process, including EMT. Like protein-coding genes, ncRNAs can be deregulated in cancer, acting as oncogenes or tumor suppressors. The various forms of ncRNAs, including microRNAs, PIWI-interacting RNAs, small nucleolar RNAs, transfer RNA-derived RNA fragments, long non-coding RNAs, and circular RNAs can orchestrate the complex regulatory networks of EMT at multiple levels. Understanding the molecular mechanism underlying ncRNAs in EMT can provide fundamental insights into cancer metastasis and may lead to novel therapeutic approaches. In this review, we describe recent advances in the understanding of ncRNAs in EMT and provide an overview of recent ncRNA applications in the clinic.

• CCAT1
• CREB1
• EMT
• NF-κB pathway
• cell cycle
• cell plasticity

• AKAP
• GSK3
• GSKIP
• PKA
• PKA–GSKIP–GSK3 axis

In response to vascular injury vascular smooth muscle cells (VSMCs) alternate between a differentiated (contractile) and a dedifferentiated (synthetic) state or phenotype. Although parts of the signaling cascade regulating the phenotypic switch have been described, the role of miRNAs is still incompletely understood. To systematically address this issue, we have established a microscopy-based quantitative assay and identified 23 miRNAs that induced contractile phenotypes when over-expressed. These were then correlated to miRNAs identified from RNA-sequencing when comparing cells in the contractile and synthetic states. Using both approaches, six miRNAs (miR-132-3p, miR-138-5p, miR-141-3p, miR-145-5p, miR-150-5p, and miR-22-3p) were filtered as candidates that induce the phenotypic switch from synthetic to contractile. To identify potentially common regulatory mechanisms of these six miRNAs, their predicted targets were compared with five miRNAs sharing ZBTB20, ZNF704, and EIF4EBP2 as common potential targets and four miRNAs sharing 16 common potential targets. The interaction network consisting of these 19 targets and additional 18 hub targets were created to facilitate validation of miRNA-mRNA interactions by suggesting the most plausible pairs. Furthermore, the information on drug candidates was integrated into the network to predict novel combinatorial therapies that encompass the complexity of miRNAs-mediated regulation. This is the first study that combines a phenotypic screening approach with RNA sequencing and bioinformatics to systematically identify miRNA-mediated pathways and to detect potential drug candidates to positively influence the phenotypic switch of VSMCs.

The rapid increase in cancer morbidity and mortality worldwide is a major challenge for public health providers. Therefore, there is an urgent need to explore the molecular mechanism of tumorigenesis and identify potential diagnostic biomarkers and therapeutic methods. Circular RNA (circRNA) is characterized by a stable structure and tissue-specific expression; these features are useful in medical research and clinical applications. In recent years, with the development of high-throughput sequencing technology, the potential use of circRNA in cancer prognosis and treatment has been extensively explored. Abnormal circRNA expression interferes with specific signaling pathways such as the MAPK pathway; this phenomenon may provide potential diagnostic biomarkers and new therapeutic targets. The present article discusses the research progress on the regulatory roles of MAPK/ERK pathway-related circRNA molecules in the development and progression of different types of tumors. This review may provide insight into the development of circRNA-based cancer management strategies.

• MAPK signaling
• cancer
• circular RNA
• non-coding RNA
• tumor drug resistance

• Wnt signaling
• cancer management
• colorectal cancer
• mcroRNA

• Cancer stem cells
• Claudin-7
• Colorectal cancer
• Epithelial–mesenchymal transition
• Wnt/β-catenin

• Animals
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Claudins/genetics
• Claudins/metabolism
• Colorectal Neoplasms/genetics
• Epithelial-Mesenchymal Transition
• Gene Expression Regulation, Neoplastic
• Heterografts
• Humans
• Mice
• SOX9 Transcription Factor
• Wnt Signaling Pathway
• beta Catenin/metabolism

• National Natural Science Foundation of China
• Natural Science Foundation of Beijing Municipality

Exosomes are extracellular vesicles that mediate intercellular communication. They contain different molecules, such as DNA, RNA, lipid, and protein, playing essential roles in the pathogenesis of colorectal cancer (CRC). Exosomes derived from CRC are implicated in tumorigenesis, chemotherapy resistance, and metastasis. Besides, they can enhance CRC progression by increasing tumor cell proliferation, reducing apoptosis mechanistically through altering particular essential regulatory genes, or controlling several signaling pathways. Therefore, exosomes derived from CRC are essential biomarkers and can be used in the diagnosis. Indeed, it is crucial to understand the role of exosomes in CRC, which is necessary to develop diagnostic and therapeutic strategies for early detection and treatment. In the present review, we discuss the roles of exosomes in the diagnosis and treatment of CRC.

• Colorectal cancer
• Exosomes
• Biomarker
• Extracellular vesicle
• Diagnosis

MicroRNAs (miRNAs), a class of small non-coding RNAs represent potential biomarkers for colorectal cancer (CRC). The study hypothesized that miRNAs associated with liver metastases may also contribute to assessing treatment response when associated to plasma exosomes. In this study, we used two sets of biological samples, a collection of tumor tissues harvested from patients with CRC with and without liver metastases, and a collection of plasma from CRC patients with and without response to FOLFOX4/FOLFIRI regimens. We investigated 10 target miRNAs in the tissue of 28 CRC patients and identified miR-125b-5p, miR-17-5p, and miR-185-5p to be associated with liver metastasis. Further, we investigated the three miRNAs at the exosomal level in a plasma collection to test their association with chemotherapy response. Our data suggest that the elevated plasma levels of miR-17-5p and miR-185-5p could be predictive of treatment response. Overexpression of miR-17-5p and underexpression of miR-125b-5p and miR-185-5p in CRC tissue seem to be associated with metastatic potential. On the other hand, an increased expression of miR-125b-5p in plasma exosomes was potentially correlated with a more aggressive CRC phenotype.

• biomarkers
• chemotherapy response
• colorectal cancer
• exosomes
• liver metastases
• miR-125b-5p
• miR-17-5p
• miR-185-5p

• EMT
• SUFU
• Wnt/β-catenin
• hedgehog
• miRNA-150

• EMT
• extracellular vesicle
• gastrointestinal
• microRNA
• molecular signaling

• Biomarker
• Circulating miRNA
• Colorectal carcinoma
• Diagnosis
• Exosomes

• adult stem cells
• non-coding rnas

• Biomarkers
• Cell Movement
• Cell Proliferation
• Cornea/cytology
• Epithelial Cells/cytology
• Gene Expression Profiling
• Gene Regulatory Networks
• Humans
• Laser Capture Microdissection
• MicroRNAs/genetics
• Phosphatidylinositol 3-Kinases/metabolism
• Real-Time Polymerase Chain Reaction
• Sequence Analysis, RNA
• Stem Cells/cytology
• Up-Regulation

• DHRS12
• Wnt3a/β-catenin
• invasion
• osteosarcoma
• proliferation

Colorectal cancer (CRC) is one of the leading causes of cancer mortality. Angiogenesis is a rate-determining step in CRC development and metastasis. The balance of angiogenic and antiangiogenic factors is crucial in this process. Angiogenesis-related genes can be regulated post-transcriptionally by microRNAs (miRNAs) and some miRNAs have been shown to shuttle between tumor cells and the tumor microenvironment (TME). MiRNAs have context-dependent actions and can promote or suppress angiogenesis dependent on the type of cancer. On the one hand, miRNAs downregulate anti-angiogenic targets and lead to angiogenesis induction. Tumor suppressor miRNAs, on the other hand, enhance anti-angiogenic response by targeting pro-angiogenic factors. Understanding the interaction between these miRNAs and their target mRNAs will help to unravel molecular mechanisms involved in CRC progression. The aim of this article is to review the current literature on angioregulatory miRNAs in CRC.

• angiogenesis 2
• colorectal cancer 1
• microRNA 3

• HR repair
• LTR retrotransposon
• RNF169
• lncRNA
• p53

The evolutionarily conserved serine/threonine kinase Nemo-like kinase (NLK) serves an important role in cell proliferation, migration, invasion and apoptosis by regulating transcription factors among various cancers. In the present study, the function of NLK in human non-small cell lung cancer (NSCLC) was investigated. Immunohistochemical analysis and western blotting demonstrated that NLK expression was significantly reduced in NSCLC tissues compared with corresponding peritumoral tissues. Statistical analysis revealed that decreased NLK expression was associated with the presence of primary tumors, tumor node metastasis (TNM) staging, differentiation, lymph node metastasis, and E-cadherin and vimentin expression. Univariate analysis indicated that NLK expression, differentiation, lymph node metastasis, TNM stage, and E-cadherin and vimentin expression affected the prognosis of NSCLC. Cox regression analyses revealed NLK expression and TNM as independent factors that affected prognosis. Kaplan-Meier survival analysis revealed that patients with NSCLC and low NLK expression had relatively shorter durations of overall survival. In vitro, NLK overexpression inhibited A549 ncell migration and invasion as determined by wound healing and Transwell migration assays, respectively. Additionally, immunofluorescence staining indicated that downregulation of NLK expression could induce epithelial-mesenchymal transition in NSCLC. NLK knockdown significantly decreased the expression of the epithelial marker E-cadherin, and markedly increased that of β-catenin and the mesenchymal marker vimentin. Furthermore, NLK was reported to directly interact with β-catenin as determined by a co-immunoprecipitation assay. Collectively, the results of the present study indicated that decreased NLK expression could promote tumor metastasis in NSCLC.

Jatrorrhizine (JAT) is a natural protoberberine alkaloid, possesses detoxification, bactericidal and hypoglycemic activities. However, its anti-cancer mechanism is not clear. This study aimed to investigate the mechanism of JAT through which inhibits colorectal cancer in HCT-116 and HT-29 cells.

MTT assay and colony formation assay were used to check the cell proliferation ability. Cell apoptosis and cell cycle were measured by Hoechst 33342 staining and flow cytometry, respectively. Cell migration and invasion were detected by scratch wound healing assay and trans-well assay, respectively. Further, expression of related proteins was examined via Western blotting and the in vivo anti-cancer effect of JAT was confirmed by nude mice xenograft model.

The research showed that JAT inhibited the proliferation of HCT-116 and HT-29 cells with IC₅₀ values of 6.75±0.29 μM and 5.29±0.13 μM, respectively, for 72 hrs. It has also showed a time dependently, cell cycle arrested in S phase, promoted cell apoptosis and suppressed cell migration and invasion. In addition, JAT inhibited Wnt signaling pathway by reducing β-catenin and increasing GSK-3β expressions. Increased expression of E-cadherin, while decreased N-cadherin, indicating that JAT treatment suppressed the process of cell epithelial–mesenchymal transition (EMT). In HCT-116 nude mice xenograft model, JAT inhibited tumor growth and metastasis, and induced apoptosis of tumor cells.

This study demonstrated that JAT efficiently inhibited colorectal cancer cells growth and metastasis, which provides a new point for clinical treatment of colorectal cancer.

• Wnt/β-catenin signaling
• colorectal cancer (CRC)
• epithelial-mesenchymal transition (EMT)
• jatrorrhizine (JAT)
• xenograft model

Claudin 8 (CLDN8), an integral membrane protein that constitutes tight junctions in cell membranes, was recently implicated in tumor progression. However, its roles in colorectal cancer (CRC) progression and metastasis remain unknown.

In this study, we examined the effect of CLDN8 on the progression of CRC, including cell proliferation, migration, and invasion, and determines its underlying molecular mechanism using in vitro CRC cell lines and in vivo mouse xenograft models.

We found that CLDN8 expression in human CRC tissues was significantly higher than that in adjacent normal tissues. The knockdown of CLDN8 markedly suppressed the proliferation, migration, and invasion of SW480 and HT-29 CRC cells, whereas the overexpression of CLDN8 notably promoted tumor progression in SW480 and HT-29 CRC cells. Mechanistic studies revealed that CLDN8 upregulated p-ERK (p-PKB/AKT) and MMP9 in CRC cells. Notably, the MAPK/ERK inhibitor PD98095 dramatically attenuated the effects of CLDN8 on p-ERK and MMP9. Moreover, PD98095 remarkably blocked the tumor-promoting activity of CLDN8. The knockdown of CLDN8 also inhibited the in vivo tumor growth in a nude mouse xenograft model. Collectively, CLDN8 promoted CRC cell proliferation, migration, and invasion, at least in part, by activating the MAPK/ERK signaling pathway.

These findings suggest that CLDN8 exhibits an oncogenic effect in human CRC progression.

• CLDN8
• MAPK/ERK signaling
• colorectal cancer

• epithelial-mesenchymal transition
• microRNA-150
• prostate cancer
• transient receptor potential melastatin 4
• β-catenin signaling pathway

• Aged
• Animals
• Epithelial-Mesenchymal Transition/physiology
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/biosynthesis
• MicroRNAs/genetics
• Middle Aged
• Neoplasm Invasiveness/pathology
• Prostatic Neoplasms/genetics
• Prostatic Neoplasms/metabolism
• Prostatic Neoplasms/pathology
• Signal Transduction/physiology
• TRPM Cation Channels/antagonists & inhibitors
• TRPM Cation Channels/biosynthesis
• TRPM Cation Channels/genetics
• beta Catenin/antagonists & inhibitors
• beta Catenin/biosynthesis
• beta Catenin/genetics

• colorectal cancer
• exosomes
• liver
• metastases
• miRNAs

miR‐372/373, a cluster of stem cell‐specific microRNAs transactivated by the Wnt pathway, has been reported to be dysregulated in various cancers, particularly colorectal cancer (CRC); however, the unique role of these microRNAs in cancer remains to be discovered. In the present study, we characterized the upregulation in expression of miR‐372/373 in CRC tissues from The Cancer Genome Atlas data, and then showed that overexpression of miR‐372/373 enhanced the stemness of CRC cells by enriching the CD26/CD24‐positive cell population and promoting self‐renewal, chemotherapy resistance and the invasive potential of CRC cells. To clarify the mechanism underlying microRNA‐induced stemness, we profiled 45 cell signaling pathways in CRC cells overexpressing miR‐372/373 and found that stemness‐related pathways, such as Nanog and Hedgehog, were upregulated. Instead, differentiation‐related pathways, such as NFκB, MAPK/Erk and VDR, were markedly repressed by miR‐372/373. Numerous new targets of miR‐372/373 were identified, including SPOP, VDR and SETD7, all of which are factors important for cell differentiation. Furthermore, in contrast to the increase in miR‐372/373 expression in CRC tissues, the expression levels of SPOP and VDR mRNA were significantly downregulated in these tissues, indicative of the poor differentiation status of CRC. Taken together, our findings suggest that miR‐372/373 enhance CRC cell stemness by repressing the expression of differentiation genes. These results provide new insights for understanding the function and mechanisms of stem cell‐specific microRNAs in the development of metastasis and drug resistance in CRC.

• NFκB
• SPOP
• VDR
• cancer stem cell
• colorectal cancer
• miR-372/373

• Colorectal cancer
• Epithelial-to-mesenchymal transition
• Pimozide
• Wnt/β‑catenin

MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs that can post-transcriptionally regulate the expression of various oncogenes and tumor suppressor genes. Dysregulated expression of many miRNAs have been shown to mediate the signaling pathways critical in the multistep carcinogenesis of colorectal cancer (CRC). MiRNAs are stable and protected from RNase-mediated degradation, thereby enabling its detection in biological fluids and archival tissues for biomarker studies. This review focuses on the role and application of miRNAs in the prognosis and therapy of CRC. While stage II CRC is potentially curable by surgical resection, a significant percentage of stage II CRC patients do develop recurrence. MiRNA biomarkers may be used to stratify such high-risk population for adjuvant chemotherapy to provide better prognoses. Growing evidence also suggests that miRNAs are involved in the metastatic process of CRC. Certain of these miRNAs may thus be used as prognostic biomarkers to identify patients more likely to have micro-metastasis, who could be monitored more closely after surgery and/or given more aggressive adjuvant chemotherapy. Intrinsic and acquired resistance to chemotherapy severely hinders successful chemotherapy in CRC treatment. Predictive miRNA biomarkers for response to chemotherapy may identify patients who will benefit the most from a particular regimen and also spare the patients from unnecessary side effects. Selection of patients to receive the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Lastly, forced expression of tumor suppressor miRNA or silencing of oncogenic miRNA in tumors by gene therapy can also be adopted to treat CRC alone or in combination with other chemotherapeutic drugs.

• MicroRNA
• Colorectal cancer
• Multidrug resistance
• Prognosis
• Therapeutic target
• Apoptosis
• Metastasis
• Recurrence
• Risk stratification

• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/antagonists & inhibitors
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Carcinogenesis/genetics
• Chemotherapy, Adjuvant/methods
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/therapy
• Gene Expression Regulation, Neoplastic
• Gene Silencing
• Genetic Therapy/methods
• Humans
• MicroRNAs/analysis
• MicroRNAs/antagonists & inhibitors
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplasm Recurrence, Local/genetics
• Neoplasm Recurrence, Local/prevention & control
• Neoplasm Staging
• Patient Selection
• Prognosis
• Signal Transduction/genetics
• Translational Research, Biomedical/trends

• AKT/mTOR
• EMT
• HCC
• Wnt/β-catenin
• lncRNA OGFRP1

• AKT
• CREB
• Cornea
• Tissue-engineering
• Wound healing

The aim of the present study was to examine the diagnosis of methylation of CDX2 gene promoter in colorectal cancer (CRC) and assessed its value in the prediction of treatment efficacy. Sixty patients who were diagnosed as CRCs for the first time, 60 patients with hyperplastic polyps (HPs) and adenomas, and 60 patients with inflammatory lesions or healthy patients (control group) were included in the present study. The methylation levels of CDX2 gene promoter were detected by methylation-specific polymerase chain reaction (MSP), and the expression levels of CDX2 mRNA were detected by fluorescence quantitative PCR. Treatment options, such as surgery, radiotherapy and chemotherapy, were chosen on the basis of TNM staging of CRC patients. The tumor-free survival, relapse rate and mortality were also recorded. The methylation rate was 71.67% (43/60) and significantly higher in the CRC group as compared to the HP/adenoma and control groups, P<0.05. Moreover, they showed further increase with higher degree of TNM staging. The expression levels of CDX2 mRNA was significantly lower in the CRC group in comparison to HP/adenoma and control groups, P<0.05, and showed a further decrease with a higher degree of TNM staging. The tumor-free survival was shorter, and the relapse rate and mortality were higher in patients with positive methylation in the CRC group, P<0.05. Multivariate logistic regression analysis demonstrated that TNM staging and positive methylation were independent risk factors of mortality. In conclusion, higher methylation degree of CDX2 gene promoter resulted in decreased expression of CDX2 gene, and was closely associated with TNM staging and prognosis. TNM staging and positive methylation were independent risk factors of mortality for CRC patients.

• CDX2 gene
• colorectal cancer
• methylation of promoter

Growing evidence suggests that miR-150 plays an inhibitory role in various types of cancer. However, the function and underlying mechanisms of miR-150 in triple-negative breast cancer (TNBC) remain unknown.

miR-150 expression was detected by qRT-PCR and ISH in TNBC tumor and adjacent normal breast tissues. miR-150 function was analyzed by wound healing and transwell assay in vitro and mouse lung metastasis model in vivo. mRNA microarray, qRT-PCR, western blotting and luciferase assay were used to identify the target gene of miR-150. HMGA2 over-expression plasmid was co-transfected with miR-150 to study the role of miR-150 through regulating HMGA2.

We found that miR-150 was down-regulated in TNBC tumor tissues compared to corresponding adjacent, normal breast tissues, and was correlated with decreased lymph-node metastasis. Ectopic expression of miR-150 suppressed TNBC cell migration in vitro and metastasis in vivo. Mechanistic study revealed that miR-150 down-regulates HMGA2 by directly targeting its mRNA. Moreover, the suppression of cell migration caused by miR-150 is relieved by over-expression of HMGA2, suggesting that miR-150 inhibits migration of TNBC cells by down-regulating HMGA2.

This work indicates that the miR-150/HMGA2 axis may serve as a treatment marker in TNBC.

• HMGA2
• metastasis
• miR-150
• triple-negative breast cancer

Hepatocellular carcinoma (HCC) ranks the sixth most common cancer and the third cause of cancer-related mortality worldwide. Recent studies identified that circ-ITCH Suppresses mutiple cancers proliferation via inhibiting the Wnt/beta-Catenin pathway. In current study, conducted a genetic association study together with epidemiological follow-up study to delineate the role of circ-ITCH in the development and progression of HCC. we found rs10485505 (adjusted OR =1.18; 95% CI=1.06-1.31; P value =3.1×10^-3) and rs4911154 (adjusted OR =1.27; 95% CI=1.14-1.43; P value =3.7×10^-5) were significantly associated with increased HCC risk. The expression level of circ-ITCH was significantly lower in HCC tissues, compared with that in adjacent tissues (P value < 0.001). Cox regression analysis indicated that high expression of circ-ITCH was associated with favorable survival of HCC (HR=0.45; 95% CI=0.29-0.68; P value < 0.001). These results indicate that circ-ITCH may have an inhibitory effect on HCC, and could serve as susceptibility and prognostic biomarkers for HCC patients.

• circ-ITCH
• hepatocellular carcinoma
• survival
• susceptibility

• CEMIP
• Colorectal cancer
• EMT
• Wnt/β-catenin/Snail signaling

• EMT
• colorectal cancer
• metastasis

Mounting evidence has indicated microRNA (miR) dysregulation and the Wnt/β-catenin signaling pathway jointly drive carcinogenesis, cancer metastasis, and drug-resistance. The current review will focus on the role of the crosstalk between miRs and the Wnt/β-catenin signaling pathway in cancer development. MiRs were found to activate or inhibit the canonical Wnt pathway at various steps. On the other hand, Wnt activation increases expression of miR by directly binding to its promoter and activating transcription. Moreover, there are mutual feedback loops between some miRs and the Wnt/β-catenin signaling pathway. Clinical trials of miR-based therapeutic agents are investigated for solid and hematological tumors, however, challenges concerning low bioavailability and possible side effects must be overcome before the final clinical application. This review will describe current understanding of miR crosstalk with the Wnt/β-catenin signaling cascade. Better understanding of the regulatory network will provide insight into miR-based therapeutic development.

• Wnt/β-catenin signaling pathway
• cancer
• microRNA

The alveolar-capillary barrier is composed of epithelial and endothelial cells interacting across a fibrous extracelluar matrix (ECM). Although remodeling of the ECM occurs during several lung disorders, it is not known how fiber structure and mechanics influences cell injury during cyclic airway reopening as occurs during mechanical ventilation (atelectrauma). We have developed a novel in vitro platform that mimics the micro/nano-scale architecture of the alveolar microenvironment and have used this system to investigate how ECM microstructural properties influence epithelial cell injury during airway reopening. In addition to epithelial-endothelial interactions, our platform accounts for the fibrous topography of the basal membrane and allows for easy modulation of fiber size/diameter, density and stiffness. Results indicate that fiber stiffness and topography significantly influence epithelial/endothelial barrier function where increased fiber stiffness/density resulted in altered cytoskeletal structure, increased tight junction (TJ) formation and reduced barrier permeability. However, cells on rigid/dense fibers were also more susceptible to injury during airway reopening. These results indicate that changes in the mechanics and architecture of the lung microenvironment can significantly alter cell function and injury and demonstrate the importance of implementing in vitro models that more closely resemble the natural conditions of the lung microenvironment.

Alpha B-crystallin (HspB5) is abnormally expressed in tumor tissues and portends a poor prognosis in cancer patients. However, the role of HspB5 in colorectal cancer (CRC) is still unclear. Seventy CRC patients and 40 healthy volunteers were sampled from August 2012 to March 2015 in order to determine the clinical significance of HspB5. In vitro cellular studies were used to validate its molecular mechanisms in CRC. Our clinical data indicated that HspB5 was up-regulated, and had a positive association with TNM stage CRC patients. The expression level of HspB5 in CRC patients was closely correlated with MMP7 and E-cadherin, two core epithelial–mesenchymal transition (EMT) gene products. The in vitro studies revealed that high HspB5 expression could prompt tumor cell proliferation and invasion, as well as EMT. Gene-microarray analysis suggested three significant signaling pathways (PI3K, p38 and ERK) were involved in HspB5-induced EMT. Signal transduction pathway inhibitors and HspB5 gene knockdown models suggested that HspB5 promotes CRC tumorigenesis and EMT progression through ERK signaling pathways. In summary, HspB5 maybe trigger the EMT in CRC by activating the ERK signaling pathway. It is a potential tumor biomarker for CRC diagnosis and prognosis.