Matrin-3 acts as a potential biomarker and promotes hepatocellular carcinoma progression by interacting with cell cycle-regulating genes.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The oncogenic role of Matrin-3 (MATR3), an a nuclear matrix protein, in HCC remains largely unknown. Here, we document the biological function of MATR3 in HCC based on integrated bioinformatics analysis and functional studies. According to the TCGA database, MATR3 expression was found to be positively correlated with clinicopathological characteristics in HCC. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve displayed the diagnostic and prognostic potentials of MATR3 in HCC patients, respectively. Pathway enrichment analysis represented the enrichment of MATR3 in various molecular pathways, including the regulation of the cell cycle. Functional assays in HCC cell lines showed reduced proliferation of cells with stable silencing of MATR3. At the same time, the suppressive effects of MATR3 depletion on HCC development were verified by xenograft tumor experiments. Moreover, MATR3 repression also resulted in cell cycle arrest by modulating the expression of cell cycle-associated genes. In addition, the interaction of MATR3 with cell cycle-regulating factors in HCC cells was further corroborated with co-immunoprecipitation and mass spectrometry (Co-IP/MS). Furthermore, CIBERSORT and TIMER analyses showed an association between MATR3 and immune infiltration in HCC. In general, this study highlights the novel oncogenic function of MATR3 in HCC, which could comprehensively address how aberrant changes in the cell cycle promote HCC development. MATR3 might serve as a prognostic predictor and therapeutic target for HCC patients.

The efficient of application of a fine magnetic traction system simplifies colorectal endoscopic submucosal dissection: A porcine study.

BACKGROUND: Sometimes it is difficult to maintain good visualization of the submucosal layer during colorectal endoscopic submucosal dissection (ESD). This study aimed to evaluate the feasibility and efficacy of a novel traction method, the fine magnetic traction system (FMTS), in colorectal ESD. METHODS: ESD was performed 10, 15, or 30 cm from the anus in the colorectums of 10 Bama miniature pigs with or without FMTS. The circumcision and dissection per unit time (cm2/min), en bloc resection, perforation and bleeding rates, size and integrity of the specimen and submucosal injection times were analysed. RESULTS: A total of 60 ESD procedures were performed with or without FMTS assistance. The en bloc resection rates were 100% at 10 and 15 cm from the anus in both the control group (conventional ESD) and the FMTS group. However, at 30 cm from the anus, these rates were only 10% and 70% (p = 0.006). The resection speeds (control vs. FMTS) at the 10, 15, and 30 cm points were 0.35 ± 0.07 cm2/min vs. 0.39 ± 0.19 cm2/min (p = 0.56), 0.30 ± 0.09 cm2/min vs. 0.38 ± 0.02 cm2/min (p = 0.04), and 0.11 cm2/min vs. 0.26 ± 0.10 cm2/min, respectively. CONCLUSIONS: The FMTS provides effective counter-traction and efficiently reduces the risks and difficulties of difficult colonic ESD in the porcine model.

miR-497 defect contributes to gastric cancer tumorigenesis and progression via regulating CDC42/ITGB1/FAK/PXN/AKT signaling.

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. MicroRNAs (miRNAs) are known to be important regulators of GC. This study aims to investigate the role of miRNA (miR)-497 in GC. We demonstrated that the expression of miR-497 was downregulated in human GC tissues. After N-methyl-N-nitrosourea treatment, the incidence of GC in miR-497 knockout mice was significantly higher than that in wild-type mice. miR-497 overexpression suppressed GC cell proliferation, cell-cycle progression, colony formation, anti-apoptosis ability, and cell migration and invasion capacity. Additionally, miR-497 overexpression decreased the expression levels of cell division cycle 42 (CDC42) and integrin ß1 (ITGB1) and inhibited the phosphorylation of focal adhesion kinase (FAK), paxillin (PXN), and serine-threonine protein kinase (AKT). Furthermore, overexpression of miR-497 inhibited the metastasis of GC cells in vivo, which could be counteracted by CDC42 restoration. Furthermore, the focal adhesion of GC cells was found to be regulated by miR-497/CDC42 axis via ITGB1/FAK/PXN/AKT signaling. Collectively, it is concluded that miR-497 plays an important role in the repression of GC tumorigenesis and progression, partly via the CDC42/ITGB1/FAK/PXN/AKT pathway.

Low microRNA150 expression is associated with activated carcinogenic pathways and a poor prognosis in patients with breast cancer.

Breast cancer is the most common type of cancer amongst women worldwide, and numerous microRNAs (miRNAs/miRs) are involved in the initiation and progression of breast cancer. The aim of the present study was to identify hub miRNAs and determine the underlying mechanisms regulated by these miRNAs in breast cancer. Breast invasive carcinoma transcriptome data (including mRNAs and miRNAs), and clinical data were acquired from The Cancer Genome Atlas database. Differential gene expression analysis, co­expression network analysis, gene set enrichment analysis (GSEA) and prognosis analysis were used to screen the hub miRNAs and explore their functions. Functional experiments were used to determine the underlying mechanisms of the hub miRNAs in breast cancer cells. The results revealed that low miR150 expression predicted a more advanced disease stage, and was associated with a less favorable prognosis. Through the combined use of five miRNA­target gene prediction tools, 31 potential miR150 target genes were identified. GSEA revealed that low miR150 expression was associated with the upregulation of several cancer­associated signaling pathways, and the downregulation of several tumor suppressor genes. Furthermore, miR150 independently affected overall survival in patients, and interacted with its target genes to indirectly affect overall and disease­free survival. Functional experiments demonstrated that miR150 positively regulated B and T lymphocyte attenuator (BTLA), and the downregulation of miR150 and BTLA combined promoted cell migration. In conclusion, the present study revealed that low miR150 expression was associated with less favorable clinical features, upregulation of several carcinogenic signaling pathways, and poor patient survival. Additionally, a miR150­BTLA axis was suggested to regulate cell viability and migration.

CXCL12 and IL7R as Novel Therapeutic Targets for Liver Hepatocellular Carcinoma Are Correlated With Somatic Mutations and the Tumor Immunological Microenvironment.

The mechanism of liver hepatocellular carcinoma (LIHC) development in correlation with tumor microenvironments and somatic mutations is still being elucidated. This study aims to identify the potential molecular mechanisms and candidate biomarkers in response to tumor microenvironments and somatic mutations. Multiple bioinformatics analysis methods were applied to assess the tumor immunological microenvironment, differentially expressed genes, genetic function enrichment, immunocyte infiltration, regulatory network construction, and tumor mutational burden, and to identify DNA methylation sites. The immunological microenvironment features of ESTIMATE score (OS: p = 0.017, HR = 0.64; RFS: HR = 0.43, p < 0.001) have an important impact on the prognosis of LIHC patients. Cut-off by ESTIMATE score and prognostic information identified 666 DEGs (45 downregulated and 621 upregulated) that were linked with leukocyte migration and lymphocyte activation. In immunocyte infiltration analysis, NK cells (resting), M1 macrophages, CD8+ T cells, and regulatory T cells (Tregs), which are considered core immunoregulatory cells, exhibited significant differences between higher and lower ESTIMATE scores (overall survival and recurrence-free survival p-values < 0.01). Subsequently, further analysis of immunocyte-hub gene identification illustrated that the expression levels of CXCL12 and IL7R significantly correlated with core immunoregulatory cells and somatic mutations (CXCL12: p = 2.1E-06; IL7R: p = 0.001). This study provides new insight into our understanding of the mechanisms of immunocyte regulation and microenvironment involved in LIHC development as well as the effective biomarkers of CXCL12 and IL7R and core immunoregulatory cells, which may emerge as novel therapies for LIHC patients.

Identification of a Set of Genes Improving Survival Prediction in Kidney Renal Clear Cell Carcinoma through Integrative Reanalysis of Transcriptomic Data.

BACKGROUND: With an enormous amount of research concerning kidney cancer being conducted, various treatments have been applied to its cure. However, high recurrence and metastasis rates continue to pose a threat to the survival of patients with kidney renal clear cell carcinoma (KIRC). METHODS: Data from The Cancer Genome Atlas were downloaded, and a series of analyses were performed, including differential analysis, Cox analysis, weighted gene coexpression network analysis, least absolute shrinkage and selection operator analysis, multivariate Cox analysis, survival analysis, and receiver operating characteristic curve and functional enrichment analysis. RESULTS: A total of 5,777 differentially expressed genes were identified from the differential analysis. The Cox analysis showed 1,853 significant genes (P < 0.01). Weighted gene coexpression network analysis revealed that 226 genes in the module were related to clinical parameters, including Tumor-Node-Metastasis (TNM) staging. Least absolute shrinkage and selection operator and multivariate Cox analyses suggested that four genes (CDKL2, LRFN1, STAT2, and SOWAHB) had a potential function in predicting the survival time of patients with KIRC. Survival analysis uncovered that a high risk of these four genes was associated with an unfavorable prognosis. Receiver operating characteristic curve analysis further confirmed the accuracy of the risk score model. The analysis of clinicopathological parameters of the four identified genes revealed that they were associated with the progression of KIRC. CONCLUSION: The gene expression model consisting of CDKL2, LRFN1, STAT2, and SOWAHB is a promising tool for predicting the prognosis of patients with KIRC. The results of this study may provide insights into the diagnosis and treatment of KIRC.

AGXT2L1 is downregulated in carcinomas of the digestive system.

Alanine-glyoxylate aminotransferase 2-like 1 (AGXT2L1) is a modulator of phospholipid metabolism, and its role in tumor biology is obscure. Previously, significant downregulation of AGXT2L1 has been observed in hepatocellular carcinoma. The aim of the present study was to investigate AGXT2L1 expression and its association with the clinical characteristics of common carcinomas of the digestive system. In the present study, the expression levels of AGXT2L1 were detected by immunohistochemical staining in colorectal cancer (CRC), gastric cancer and pancreatic cancer tissues. The associations between AGXT2L1 expression and clinicopathological features were analyzed using public gene expression datasets. Small interfering RNA was transfected into SW480 and HCT116 cells to explore the role of AGXT2L1 in CRC cells. AGXT2L1 expression was significantly decreased in cancerous tissues compared with in normal tissues, and low AGXT2L1 expression was associated with an unfavorable prognosis in patients. Furthermore, it was revealed that AGXT2L1 may regulate phosphatidylinositol and phosphatidylserine metabolism in cancerous tissues, and that decreased AGXT2L1 expression could induce autophagy in CRC cells. Overall, the present study provides a basis for further understanding of the role of AGXT2L1 and its association with autophagy in cancer.

MFAP2 is overexpressed in gastric cancer and promotes motility via the MFAP2/integrin α5ß1/FAK/ERK pathway.

Gastric cancer (GC) is one of the most common malignancies and its prognosis is extremely poor. This study identifies a novel oncogene, microfibrillar-associated protein 2 (MFAP2) in GC. With integrative reanalysis of transcriptomic data, we found MFAP2 as a GC prognosis-related gene. And the aberrant expression of MFAP2 was explored in GC samples. Subsequent experiments indicated that silencing and exogenous MFAP2 could affect motility of cancer cells. The inhibition of silencing MFAP2 could be rescued by another FAK activator, fibronectin. This process is probably through affecting the activation of focal adhesion process via modulating ITGB1 and ITGA5. MFAP2 regulated integrin expression through ERK1/2 activation. Silencing MFAP2 by shRNA inhibited tumorigenicity and metastasis in nude mice. We also revealed that MFAP2 is a novel target of microRNA-29, and miR-29/MFAP2/integrin α5ß1/FAK/ERK1/2 could be an important oncogenic pathway in GC progression. In conclusion, our data identified MFAP2 as a novel oncogene in GC and revealed that miR-29/MFAP2/integrin α5ß1/FAK/ERK1/2 could be an important oncogenic pathway in GC progression.

Understanding optical reflectance contrast for real-time characterization of epithelial precursor lesions.

Detecting early-stage epithelial cancers and their precursor lesions are challenging as lesions could be subtle and focally or heterogeneously distributed over large mucosal areas. Optical coherence tomography (OCT) that enables wide-field imaging of subsurface microstructures in vivo is a promising screening tool for epithelial diseases. However, its diagnostic capability has not been fully appreciated since the optical reflectance contrast is poorly understood. We investigated the back-scattered intensities from clustered or packed nanometer scale intracellular scatterers using finite-difference time-domain method and 1-µm resolution form of OCT, and uncovered that there existed correlations between the reflectance contrasts and the ultrastructural clustering or packing states of these scatterers, which allows us to interpret the physiological state of the cells. Specifically, both polarized goblet cells and foveolar cells exhibited asymmetric reflectance contrast, but they could be differentiated by the optical intensity of the mucin cup due to the different ultrastructural make-ups of the mucin granules; keratinocytes could demonstrate varied cytoplasmic intensity and their cytoplasmic contrast was closely correlated with the packing state of keratin filaments. Further preliminary study demonstrated that these new understandings of OCT image contrast enables the characterization of precancerous lesions, which could complement the current morphology-based criteria in realizing "virtual histology" and would have a profound impact for the screening and surveillance of epithelial cancers.

Rapid, High-Resolution, Label-Free, and 3-Dimensional Imaging to Differentiate Colorectal Adenomas and Non-Neoplastic Polyps With Micro-Optical Coherence Tomography.

INTRODUCTION: "Resect and discard" paradigm is one of the main strategies to deal with colorectal diminutive polyps after optical diagnosis. However, there are risks that unrecognized potentially malignant lesions are discarded without accurate diagnosis. The purpose of this study is to validate the potential of micro-optical coherence tomography (µOCT) to improve the diagnostic accuracy of colorectal lesions and help endoscopists make better clinical decision without additional pathology costs. METHODS: Fresh tissue samples were obtained from patients with colorectal polyps or colorectal cancer who received endoscopic therapy or laparoscopic surgery. These samples were instantly imaged by µOCT and then sent to pathological evaluation. Then, µOCT images were compared with corresponding HE sections. We created consensus µOCT image criteria and then tested to determine sensitivity, specificity, and accuracy of our system to discriminate neoplastic polyps from non-neoplastic polyps. RESULTS: Our µOCT system achieved a resolution of 2.0 µm in both axial and lateral directions, clearly illustrated both cross-sectional and en face subcellular-level microstructures of colorectal lesions ex vivo, demonstrating distinctive patterns for inflammatory granulation tissue, hyperplastic polyp, adenoma, and cancerous tissue. For the 58 cases of polyps, the accuracy of the model was 94.83% (95% confidence interval [CI], 85.30%-98.79%), the sensitivity for identification of adenomas was 96.88% (95% CI, 82.89%-99.99%), and the specificity was 92.31% (95% CI, 74.74%-98.98%). Our diagnostic criteria could help both expert endoscopists and nonexpert endoscopists to identify neoplastic from non-neoplastic polyps with satisfactory accuracy and good interobserver agreement. DISCUSSION: We propose a new strategy using µOCT to differentiate benign polyps and adenomas after the lesions are resected. The application of µOCT can potentially reduce the cost of pathological examination and minimize the risk of discarding malignant lesions during colonosocpy examination.

Contrast of nuclei in stratified squamous epithelium in optical coherence tomography images at 800 nm.

Imaging nuclei of keratinocytes in the stratified squamous epithelium has been a subject of intense research since nucleus associated cellular atypia is the key criteria for the screening and diagnosis of epithelial cancers and their precursors. However, keratinocyte nuclei have been reported to be either low scattering or high scattering, so that these inconsistent reports might have led to misinterpretations of optical images, and more importantly, hindered the establishment of optical diagnostic criteria. We disclose that they are generally low scattering in the core using Micro-optical coherence tomography (µOCT) of 1.28-µm axial resolution in vivo; those previously reported "high scattering" or "bright" signals from nuclei are likely from the nucleocytoplasmic boundary, and the low-scattering nuclear cores were missed possibly due to insufficient axial resolutions (~4µm). It is further demonstrated that the high scattering signals may be associated with flattening of nuclei and cytoplasmic glycogen accumulation, which are valuable cytologic hallmarks of cell maturation.

Randomised controlled trial of WISENSE, a real-time quality improving system for monitoring blind spots during esophagogastroduodenoscopy.

OBJECTIVE: Esophagogastroduodenoscopy (EGD) is the pivotal procedure in the diagnosis of upper gastrointestinal lesions. However, there are significant variations in EGD performance among endoscopists, impairing the discovery rate of gastric cancers and precursor lesions. The aim of this study was to construct a real-time quality improving system, WISENSE, to monitor blind spots, time the procedure and automatically generate photodocumentation during EGD and thus raise the quality of everyday endoscopy. DESIGN: WISENSE system was developed using the methods of deep convolutional neural networks and deep reinforcement learning. Patients referred because of health examination, symptoms, surveillance were recruited from Renmin hospital of Wuhan University. Enrolled patients were randomly assigned to groups that underwent EGD with or without the assistance of WISENSE. The primary end point was to ascertain if there was a difference in the rate of blind spots between WISENSE-assisted group and the control group. RESULTS: WISENSE monitored blind spots with an accuracy of 90.40% in real EGD videos. A total of 324 patients were recruited and randomised. 153 and 150 patients were analysed in the WISENSE and control group, respectively. Blind spot rate was lower in WISENSE group compared with the control (5.86% vs 22.46%, p<0.001), and the mean difference was -15.39% (95% CI -19.23 to -11.54). There was no significant adverse event. CONCLUSIONS: WISENSE significantly reduced blind spot rate of EGD procedure and could be used to improve the quality of everyday endoscopy. TRIAL REGISTRATION NUMBER: ChiCTR1800014809; Results.

Apatinib Promotes Apoptosis of Pancreatic Cancer Cells through Downregulation of Hypoxia-Inducible Factor-1α and Increased Levels of Reactive Oxygen Species.

At present, apatinib is considered a new generation agent for the treatment of patients with gastric cancer. However, the effects of apatinib on pancreatic cancer have not been clarified. This study investigated the impact of apatinib on the biological function of pancreatic cancer cells and the potential mechanism involved in this process. Using the Cell Counting Kit-8 method, we confirmed that apatinib treatment inhibited cell proliferation in vitro. Moreover, the migration rate of pancreatic cells was inhibited. The effects of apatinib on apoptosis and cell cycle distribution of pancreatic carcinoma cells were detected by flow cytometry. The number of apoptotic cells was significantly increased, and the cell cycle was altered. Furthermore, we demonstrated that apatinib inhibited the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor, and markers of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathway, which increased the levels of reactive oxygen species in vitro. Apatinib significantly inhibited the biological function of pancreatic cancer cells. It promoted apoptosis, downregulated the expression of HIF-1α, and increased the levels of reactive oxygen species.

A deep neural network improves endoscopic detection of early gastric cancer without blind spots.

BACKGROUND: Gastric cancer is the third most lethal malignancy worldwide. A novel deep convolution neural network (DCNN) to perform visual tasks has been recently developed. The aim of this study was to build a system using the DCNN to detect early gastric cancer (EGC) without blind spots during esophagogastroduodenoscopy (EGD). METHODS: 3170 gastric cancer and 5981 benign images were collected to train the DCNN to detect EGC. A total of 24549 images from different parts of stomach were collected to train the DCNN to monitor blind spots. Class activation maps were developed to automatically cover suspicious cancerous regions. A grid model for the stomach was used to indicate the existence of blind spots in unprocessed EGD videos. RESULTS: The DCNN identified EGC from non-malignancy with an accuracy of 92.5 %, a sensitivity of 94.0 %, a specificity of 91.0 %, a positive predictive value of 91.3 %, and a negative predictive value of 93.8 %, outperforming all levels of endoscopists. In the task of classifying gastric locations into 10 or 26 parts, the DCNN achieved an accuracy of 90 % or 65.9 %, on a par with the performance of experts. In real-time unprocessed EGD videos, the DCNN achieved automated performance for detecting EGC and monitoring blind spots. CONCLUSIONS: We developed a system based on a DCNN to accurately detect EGC and recognize gastric locations better than endoscopists, and proactively track suspicious cancerous lesions and monitor blind spots during EGD.

SSRP1 promotes colorectal cancer progression and is negatively regulated by miR-28-5p.

In this study, microarray data analysis, real-time quantitative PCR and immunohistochemistry were used to detect the expression levels of SSRP1 in colorectal cancer (CRC) tissue and in corresponding normal tissue. The association between structure-specific recognition protein 1 (SSRP1) expression and patient prognosis was examined by Kaplan-Meier analysis. SSRP1 was knocked down and overexpressed in CRC cell lines, and its effects on proliferation, cell cycling, migration, invasion, cellular energy metabolism, apoptosis, chemotherapeutic drug sensitivity and cell phenotype-related molecules were assessed. The growth of xenograft tumours in nude mice was also assessed. MiRNAs that potentially targeted SSRP1 were determined by bioinformatic analysis, Western blotting and luciferase reporter assays. We showed that SSRP1 mRNA levels were significantly increased in CRC tissue. We also confirmed that this upregulation was related to the terminal tumour stage in CRC patients, and high expression levels of SSRP1 predicted shorter disease-free survival and faster relapse. We also found that SSRP1 modulated proliferation, metastasis, cellular energy metabolism and the epithelial-mesenchymal transition in CRC. Furthermore, SSRP1 induced apoptosis and SSRP1 knockdown augmented the sensitivity of CRC cells to 5-fluorouracil and cisplatin. Moreover, we explored the molecular mechanisms accounting for the dysregulation of SSRP1 in CRC and identified microRNA-28-5p (miR-28-5p) as a direct upstream regulator of SSRP1. We concluded that SSRP1 promotes CRC progression and is negatively regulated by miR-28-5p.

Feasibility evaluation of micro-optical coherence tomography (µOCT) for rapid brain tumor type and grade discriminations: µOCT images versus pathology.

BACKGROUND: Precise identification, discrimination and assessment of central nervous system (CNS) tumors is of critical importance to brain neoplasm treatment. Due to the complexity and limited resolutions of the existing diagnostic tools, however, it is difficult to identify the tumors and their boundaries precisely in clinical practice, and thus, the conventional way of brain neoplasm treatment relies mainly on the experiences of neurosurgeons to make resection decisions in the surgery process. The purpose of this study is to explore the potential of Micro-optical coherence tomography (µOCT) as an intraoperative diagnostic imaging tool for identifying and discriminating glioma and meningioma with their microstructure imaging ex vivo, which thus may help neurosurgeons to perform precise surgery with low costs and reduced burdens. METHODS: Fresh glioma and meningioma samples were resected from patients, and then slices of such samples were excised and imaged instantly ex vivo with a lab-built µOCT, which achieves a spatial resolution of ~ 2.0 µm (µm). The acquired optical coherence tomography (OCT) images were pathologically evaluated and compared to their corresponding histology for both tumor type and tumor grade discriminations in different cases. RESULTS: By using the lab-built µOCT, both the cross-sectional and en face images of glioma and meningioma were acquired ex vivo. Based upon the morphology results, both the glioma and meningioma types as well as the glioma grades were assessed and discriminated. Comparisons between OCT imaging results and histology showed that typical tissue microstructures of glioma and meningioma could be clearly identified and confirmed the type and grade discriminations with satisfactory accuracy. CONCLUSIONS: µOCT could provide high-resolution three-dimensional (3D) imaging of the glioma and meningioma tissue microstructures rapidly ex vivo. µOCT imaging results could help discriminate both tumor types and grades, which illustrates the potential of µOCT as an intraoperative diagnostic imaging tool to help neurosurgeons perform their surgery precisely in tumor treatment process.

Gastrin stimulates pancreatic cancer cell directional migration by activating the Gα12/13-RhoA-ROCK signaling pathway.

The mechanism by which gastrin promotes pancreatic cancer cell metastasis is unclear. The process of directing polarized cancer cells toward the extracellular matrix is principally required for invasion and distant metastasis; however, whether gastrin can induce this process and its underlying mechanism remain to be elucidated. In this study, we found that gastrin-induced phosphorylation of paxillin at tyrosine 31/118 and RhoA activation as well as promoted the metastasis of PANC-1 cancer cells. Depletion of Gα12 and Gα13 inhibited the phosphorylation of paxillin and downstream activation of GTP-RhoA, blocked the formation and aggregation of focal adhesions and facilitated polarization of actin filaments induced by gastrin. Suppression of RhoA and ROCK also exhibited identical results. Selective inhibition of the CCKBR-Gα12/13-RhoA-ROCK signaling pathway blocked the reoriented localization of the Golgi apparatus at the leading edge of migrated cancer cells. YM022 and Y-27632 significantly suppressed hepatic metastasis of orthotic pancreatic tumors induced by gastrin in vivo. Collectively, we demonstrate that gastrin promotes Golgi reorientation and directional polarization of pancreatic cancer cells by activation of paxillin via the CCKBR-Gα12/13-RhoA-ROCK signal pathway.

MORC2, a novel oncogene, is upregulated in liver cancer and contributes to proliferation, metastasis and chemoresistance.

Microrchidia 2 (MORC2) is important in DNA damage repair and lipogenesis, however, the clinical and functional role of MORC2 in liver cancer remains to be fully elucidated. The aim the present study was to clarify the role of MORC2 in liver cancer. Expression profile analysis, immunohistochemical staining, reverse transcription-quantitative polymerase chain reaction analysis and western blot analysis were performed to evaluate the levels of MORC2 in liver cancer patient specimens and cell lines; subsequently the expression of MORC2 was suppressed or increased in liver cancer cells and the effects of MORC2 on the cancerous transformation of liver cancer cells were examined in vitro and in vivo. MORC2 was upregulated in liver cancer tissues, and the upregulation was associated with certain clinicopathologic features of patients with liver cancer. MORC2 knockdown caused marked inhibition of liver cancer cell proliferation and clonogenicity, whereas the overexpression of MORC2 substantially promoted liver cancer cell proliferation. In addition, the knockdown of MORC2 inhibited the migratory and invasive ability of liver cancer cells, whereas increased migration and invasion rates were observed in cells with ectopic expression of MORC2. In a model of nude mice, the overexpression of MORC2 promoted tumorigenicity and markedly enhanced pulmonary metastasis of liver cancer. Furthermore, MORC2 regulated apoptosis and its expression level had an effect on the sensitivity of liver cancer cells to doxorubicin, 5-fluorouracil and cisplatin. Mechanically, MORC2 modulated the mitochondrial apoptotic pathway, possibly in a p53-dependent manner, and its dysregulation also resulted in the abnormal activation of the Hippo pathway. For the first time, to the best of our knowledge, the present study confirmed that MORC2 was a novel oncogene in liver cancer. These results provide useful insight into the mechanism underlying the tumorigenesis and progression of liver cancer, and offers clues into potential novel liver cancer therapies.

Aberrant high expression level of MORC2 is a common character in multiple cancers.

Microrchidia 2 (MORC2) plays important roles in DNA damage repair and lipogenesis, but the clinical and functional role of MORC2 in cancer remains largely unexplored. In this study, we showed that MORC2 was widely expressed in human tissues while significantly up-regulated in most cancer types using immunohistochemical staining and analysis of messenger RNA expression profile of more than 2000 human tissue samples from 15 different organs (lung, prostate, liver, breast, brain, stomach, colon/rectum, pancreas, ovary, endometrium, skin, nasopharynx, kidney, esophagus, and bladder). We also found that the MORC2 expression level in high-grade cancer tissues was much more elevated and associated with unfavorable pathological characteristics, poor overall survival, and disease-free survival in several kinds of cancers such as non-small cell lung cancer and breast cancer. Gene set enrichment analysis was used to predict the genes modulated by MORC2, and the results showed that dysregulation of MORC2 in tumor may take part in the cell cycle regulation and genomic instability. We observed that MORC2 knockdown would arrest the cell cycle progress, and the genome of tumors with high MORC2 expression contained more point mutations and gene copy number variation, which validates our gene set enrichment analysis results. The results also showed that MORC2 knockdown would significantly inhibit the proliferation, colony forming, migration, and invasion in multiple cancer cell lines. Taken together, these results highlight the importance of MORC2 in tumorigenesis and cancer progression, and it may act as a potential diagnostic marker and therapeutic target for these diseases.

Function of the macrophage-capping protein in colorectal carcinoma.

To investigate the role of macrophage-capping protein (CapG) in the development and progression of colorectal carcinoma (CRC), immunohistochemistry (IHC), Kaplan-Meier survival analysis, wound healing and Transwell migration assays were performed. The IHC results demonstrated that CapG was relatively highly expressed in CRC tissue compared with non-tumor tissue (P<0.001), and that the expression of CapG was significantly associated with the tumor site, differentiation, lymph node metastasis and clinical stage (P=0.021, P=0.036, P=0.012 and P=0.009, respectively). Wound healing and Transwell migration assays demonstrated that the reduction of CapG expression in a CRC cell line by RNA interference was associated with significantly impaired motility (P<0.001). Kaplan-Meier survival analysis revealed that the expression of CapG in tumor samples was not significantly associated with disease-free survival time. In conclusion, CapG was overexpressed in CRC and was associated with tumor progression; therefore, it may be a useful prognostic biomarker and therapeutic target in CRC.