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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 epidemic is worsening. Binding of the Spike1 protein of SARS-CoV-2 with the angiotensin-converting enzyme 2 (ACE2) receptor mediates entry of the virus into host cells. Many reports show that protein arginine methylation by protein arginine methyltransferases (PRMTs) is important for the functions of these proteins, but it remains unclear whether ACE2 is methylated by PRMTs. Here, we show that PRMT5 catalyses ACE2 symmetric dimethylation at residue R671 (meR671-ACE2). We indicate that PRMT5-mediated meR671-ACE2 promotes SARS-CoV-2 receptor-binding domain (RBD) binding with ACE2 probably by enhancing ACE2 N-glycosylation modification. We also reveal that the PRMT5-specific inhibitor GSK3326595 is able to dramatically reduce ACE2 binding with RBD. Moreover, we discovered that meR671-ACE2 plays an important role in ACE2 binding with Spike1 of the SARS-CoV-2 Omicron, Delta, and Beta variants; and we found that GSK3326595 strongly attenuates ACE2 interaction with Spike1 of the SARS-CoV-2 Omicron, Delta, and Beta variants. Finally, SARS-CoV-2 pseudovirus infection assays uncovered that PRMT5-mediated meR671-ACE2 is essential for SARS-CoV-2 infection in human cells, and pseudovirus infection experiments confirmed that GSK3326595 can strongly suppress SARS-CoV-2 infection of host cells. Our findings suggest that as a clinical phase II drug for several kinds of cancers, GSK3326595 is a promising candidate to decrease SARS-CoV-2 infection by inhibiting ACE2 methylation and ACE2-Spike1 interaction.

PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) is a tumor suppressor in various tumors. However, the molecular mechanism underlying PinX1’s role in cancer development and progression remains unclear. In this study, we aimed to uncover the new molecular mechanism and role of PinX1 in renal cell carcinoma (RCC) progression. We used miRNA microarray to detect the different expressed miRNAs upon PinX1 knockdown. Chromatin immunoprecipitation and Luciferase reporter assays were taken to identify the molecular mechanism of PinX1 in regulating mir-125-3p. In situ hybridization was performed to analyze the expression of mir-125a-3p in RCC using tissue microarray. The correlations between the mir-125a-3p expression level and clinicopathological features were evaluated using the χ2 test. The role and molecular mechanism of PinX1 in RCC angiogenesis were investigated through a series of in vitro and in vivo experiments. In this study, we discovered a new molecular mechanism of PinX1, in which PinX1 transcriptionally activated mir-125a-3p expression, thereby inhibiting the expression of vascular endothelial growth factor (VEGF), which is the target gene of mir-125a-3p. PinX1 also repressed tumor angiogenesis by increasing the mir-125a-3p expression in renal cancer. Moreover, the loss of mir-125a-3p expression was manifested in patients with RCC, and low miR-125a-3p levels correlated with poor survival of these patients. PinX1 represses renal cancer angiogenesis through mir-125a-3p/VEGF signal pathway. The miR-125a-3p may be a candidate clinical prognostic marker and a novel therapeutic target in RCC.

BACKGROUND Dysregulation of the splicing activator, RNA-binding motif 4 (RBM4), has recently been reported to be involved in the progression of several cancers. However, the mechanisms that underpin the activity of RBM4 in gastric cancer (GC) remain unknown. The purpose of our study was to explore how RBM4 affects the biological behavior of GC through in vivo and in vitro experiments. MATERIAL AND METHODS Western blot and flow cytometry analyses were used to investigate the RBM4 protein levels in normal gastric epithelial cells and 5 types of GC cells. Cell Counting Kit-8 assay, flow cytometry analysis, wound-healing, and migration and invasion assays were evaluated in vitro in BGC823 and MGC803 GC cells. A xenograft tumor model was used to assess whether RBM4 inhibits GC growth in vivo. Mitogen-activated protein kinase (MAPK) protein levels were determined using western blot analyses. RESULTS Our study revealed that RBM4 protein was downregulated in GC cells. Re-expression of RBM4 inhibited the proliferation, migration, and invasion of GC cells, while promoting apoptosis. Thus, the overexpression of RBM4 can inhibit tumor growth in GC mouse models. We also report that RBM4 was involved in the activation of MAPK-dependent signaling pathways in human GC. CONCLUSIONS It is hoped that these findings will improve our understanding of GC pathogenesis while also helping us to explore the feasibility of RBM4-targeted therapy for GC treatment.

CUL1 is an essential component of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. Our previous study has showed that CUL1 is positively associated with poor overall and disease-specific survival of breast cancer patients. Here, we further explored its roles in breast cancer metastasis. Our data showed that CUL1 significantly promoted breast cancer cell migration, invasion, tube formation in vitro, as well as angiogenesis and metastasis in vivo. In mechanism, the human gene expression profiling was used to determine global transcriptional changes in MDA-MB-231 cells, and we identified autocrine expression of the cytokines CXCL8 and IL11 as the target genes of CUL1 in breast cancer cell migration, invasion, metastasis, and angiogenesis. CUL1 regulated EZH2 expression to promote the production of cytokines, and finally significantly aggravating the breast cancer cell metastasis and angiogenesis through the PI3K–AKT–mTOR signaling pathway. Combined with the previous report about CUL1, we proposed that CUL1 may serve as a promising therapeutic target for breast cancer metastasis.

Renal cell carcinoma (RCC) is one of the most prevalent cancers. Long noncoding RNAs (LncRNAs) have been indicated as a mediator acted in tumorigenesis of RCC. However, the mechanism of LINC00460 on RCC is yet to be investigated. This study aimed to investigate the potential function of LINC00460 and underlying mechanism of RCC. We detected LINC00460 expression in RCC tissues and the prognosis in RCC patients using Gene Expression Profiling Interactive Analysis (GEPIA) website and The Cancer Genome Atlas (TCGA) database. LINC00460 level in normal renal cell line and RCC cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). We study the effects of LINC00460 on proliferation, migration, invasion, apoptosis in RCC cells lines using a series of in vivo and in vitro experiments. RNA sequencing (RNA-seq) analysis for the whole transcriptome was applied to searching potential LINC00460 related signal pathway in RCC. We identified the significant up-regulated expression level of LINC00460 in RCC tissues and cell lines. Elevated LINC00460 was correlated with shorter survival of RCC patients. Overexpression of LINC00460 promoted cell viability, proliferation, invasion and migration, while down-regulation of LINC00460 exerted inhibitory effect on these activities. We crucially identified that LNC00460 promotes development of RCC by influencing the PI3K/AKT pathway. Knockdown of LNC00460 decreased the phosphorylation of AKT and mTOR. The key finding of our study provided a new evidence suggesting that LINC00460 functions as an oncogene in RCC pathogenesis by mediating the PI3K/AKT pathway, which may provide a new target for the treatment of RCC.

Background As the most commonly diagnosed lung cancer, non–small cell lung carcinoma (NSCLC) is regulated by many long noncoding RNAs (lncRNAs). In the present study, we found that SH3PXD2A-AS1 expression in NSCLC tissues was upregulated compared with that in normal lung tissues in The Cancer Genome Atlas (TCGA) database. However, the role and molecular mechanism of SH3PXD2A-AS1 in NSCLC progression require further exploration. Methods The expression of SH3PXD2A-AS1 in NSCLC and normal lung tissues in a TCGA dataset was analysed by using the GEPIA website. K-M analysis was performed to explore the effects of this molecule on the survival rate in NSCLC. The functional characterization of the role and molecular mechanism of SH3PXD2A-AS1 in NSCLC was performed with a series of in vitro and in vivo experiments. Results SH3PXD2A-AS1 expression was increased in human NSCLC, and high SH3PXD2A-AS1 expression was correlated with poor overall survival. SH3PXD2A-AS1 overexpression sufficiently promoted tumour cell proliferation and accelerated cell cycle progression in vitro and tumour growth in vivo. Moreover, SH3PXD2A-AS1 interacted with DHX9 to enhance FOXM1 expression, promote tumour cell proliferation and accelerate cell cycle progression. Conclusions SH3PXD2A-AS1 promoted NSCLC growth by interacting with DHX9 to enhance FOXM1 expression. SH3PXD2A-AS1 may serve as a promising predictive biomarker for the diagnosis and prognosis of patients with NSCLC.

This study aimed to explore the role of small nucleolar RNA host gene 14 (SNHG14) in the pathogenesis of diffuse large-B-cell lymphoma (DLBCL). DLBCL cell lines (OCI-Ly7 and OCI-Ly3) and specimens from patients were collected to evaluate the roles of SNHG14 in DLBCL pathogenesis. The results showed that SNHG14 expression increased and miR-152-3p expression decreased in DLBCL tissues and cell lines, indicating a negative correlation between miR-152-3p and SNHG14 expression. Moreover, SNHG14 was found to promote DLBCL growth, migration, and EMT-like processes

Tripartite motif-containing 21 (Trim21) is mainly involved in antiviral responses and autoimmune diseases. Although Trim21 has been reported to have a cancer-promoting or anticancer effect in various tumours, its role in renal cell cancer (RCC) remains to be elucidated. In this study, we demonstrate that Trim21 is downregulated in primary RCC tissues. Low Trim21 expression in RCC is correlated with poor clinicopathological characteristics and short overall survival. Moreover, we illustrate that Trim21 inhibits RCC cells glycolysis through the ubiquitination-mediated degradation of HIF-1α, which inhibits the proliferation, tumorigenesis, migration, and metastasis of RCC cells in vitro and in vivo. Our findings show that Trim21 may become a promising predictive biomarker for the prognosis of patients with RCC.

Background. The purpose of this study was to explore the role and underlying mechanism of miR-504 and RBM4 in gastric cancer. Methods. The qRT-PCR or Western blot was performed to determine the expressions of miR-504 and RBM4 in the gastric cancer tissues and normal tissues. Human SGC-7901 cells were transfected with miR-504 mimic/inhibitor or pcDNA-RBM4. Cell proliferation and cell apoptosis were assessed by colony formation assay and flow cytometry, respectively. Luciferase reporter gene assays were used to investigate interactions between miR-504 and RBM4 in SGC-7901 cells. Results. The relative expression of miR-504 was significantly upregulated in the gastric cancer group ( n = 25 ) than in the paired normal group ( n = 25 ), but the relative RBM4 expression was remarkably downregulated in the gastric tumor group, compared with the normal group. Additionally, miR-504 overexpression increased the viability of gastric cancer cells. Moreover, RBM4 is a functional target of miR-504 in gastric cancer cells. miR-504 was further confirmed to promote SGC-7901 cell proliferation and inhibit cell apoptosis by downregulation RBM4 in vitro. Conclusions. miR-504 promotes gastric cancer cell proliferation and inhibits cell apoptosis by targeting RBM4, and this provides a potential diagnostic biomarker and treatment for patients with gastric cancer.

Long noncoding RNAs act essential regulators in lung cancer tumorigenesis. Our research aimed to investigate the potential function and molecular mechanisms of MLK7-AS1 in NSCLC (non-small-cell lung cancer). QRT-PCR results indicated that the MLK7-AS1 expression level was upregulated in NSCLC cells and tissues. MLK7-AS1 strengthened cell migration and invasion in H1299 and A549 cells. Luciferase reporter assay found that MLK7-AS1 functioned as an endogenous sponge for miR-375-3p. Transwell assay results showed that miR-375-3p suppressed cell migration and invasion in H1299 and A549 cells. YWHAZ was confirmed as a target gene of miR-375-3p by Targetscan. YWHAZ overexpression promoted the invasion of H1299 and A549 cells. MLK7-AS1 upregulated YWHAZ expression and enhanced H1299 and A549 cell invasion by sponging miR-375-3p. MLK7-AS1 improved the metastasis ability of A549 in vivo. In conclusion, MLK7-AS1 was identified as a novel oncogenic RNA in NSCLC and can function as a potential therapeutic target for NSCLC treatment.

Objectives As one of the most serious malignant carcinomas that threaten the life of sufferers constantly, gastric cancer has attracted a lot of interest among researchers. miR-34a, a member of hundreds of microRNAs (miRNAs), has been elucidated to exert a suppressive role in gastric cancer tumorgenesis based on previous extensive studies. Our study was performed with the aim to explore the functional effects of miR-34a and its predictive target programmed death ligand 1 (PDL1) in gastric cancer development. Methods We employed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western Blot analysis to investigate the regulatory effect of miR-34a on PDL1 mRNA and the corresponding protein expression. The CCK-8 and colony formation assays were used to validate the influence of the combination of miR-34a and PDL1 on the proliferation of gastric tumor cells. Meanwhile, the migration and invasion of gastric tumor cells were measured using Transwell assay. Results PDL1 was targeted and negatively modulated by miR-34a. In addition, the re-expression of miR-34a suppressed the proliferation as well as the migration and invasion of gastric tumor cells, whereas PDL1 reduced the aforementioned inhibitory effect. Conclusions PDL1 is the downstream gene of miR-34a, which can act as an anti-oncogene in gastric cancer. The miR-34a/PDL1 axis might provide a promising anticancer therapeutic approach for the clinical diagnosis, treatment, and prognosis of gastric cancer.

Gastric cancer (GC) is a multistep and multistage disease and the majority of GC cells could overexpressed one or more oncogenes. Trop2 and amphiregulin (AREG) are both overexpressed in various epithelial cell cancers and have the role in the increases tumor cells division and metastasis. However, little is known about the function and correlation of two oncogenes coexpressed in GC. The expression level of these two genes in 791 cases of GC tissues were tested, the correlations between two genes expression and clinical pathological characteristics and overall survival in GC patients through immunohistochemistry (IHC) were analyzed. This study also explored the mRNA expression level of two genes in 26 cases of freshly GC tissues by qRT‐PCR. The results indicated that Trop2+/AREG+ coexpression was higher in GC tissues than in adjacent tissues. Trop2+/AREG+ protein coexpression were associated with Tumor Node Metastasis (TNM) stage (χ 2 = 50.345, P

The present study investigated the effect of combined sorafenib chemotherapy on hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression and survival time of patients with advanced gastric cancer. From January 2010 to December 2011, 92 patients diagnosed with advanced gastric cancer were selected and randomly divided into the treatment group and control group. The treatment group was treated with sorafenib chemotherapy combined with 5-fluorouracil (5-FU), and the control group received 5-FU. The treatment course was 3–4 cycles. During the same period, 46 healthy persons admitted to the Second People's Hospital of Huaian were selected as the controls. A volume of 3–4 ml peripheral blood from each patient and control was collected before and after treatment. The expression levels of HIF-1α and VEGF in peripheral blood were measured by ELISA. The survival time of patients with advanced gastric cancer was followed and analyzed. Compared with healthy controls, serum levels of HIF-1α and VEGF were significantly higher in patients with advanced gastric cancer (P

Background Colorectal cancer (CRC) remains the fourth most common cause of cancer-related mortality worldwide. We aimed to identify key molecules and signalling pathways mediating CRC growth and metastasis. Polypyrimidine tract-binding protein 3 (PTBP3) is a member of PTB family. A prooncogenic role for PTBP3 has also been discovered in several kinds of tumors. However, the expression and biological functions of the PTBP3 are still unknown in CRC. Methods We analysed the expression levels of PTBP3 using tissue microarray containing 568 CRC tissues and corresponding non-tumor adjacent tissues. The correlations between the PTBP3 expression level and clinicopathological features were evaluated using the chi-square test. The functional characterization for the role and molecular mechanism of PTBP3 in CRC was investigated through a series of in vitro and in vivo experiments. Results We showed that PTBP3 expression was increased in human CRC, and high PTBP3 expression was correlated with poor five-year overall survival and disease-free survival. Moreover, PTBP3 promoted tumor cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. PTBP3 enhanced HIF-1α protein expression by directly binding to the 5′UTR HIF-1α mRNA and activated translation of HIF-1α. Furthermore, HIF-1α was responsible for PTBP3-induced cell migration and invasion. Conclusions PTBP3 appears to be a novel oncogene of CRC through binding to the IRES region of HIF-1α mRNA, which regulates HIF-1α translation. PTBP3 can serve as a promising predictive biomarker for recurrence and prognosis in patients with CRC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1312-y) contains supplementary material, which is available to authorized users.

Breast cancer (BC) is the most common malignant tumor in women. Although overexpression of CD155 has been detected in many types of human cancer cells, it is not completely understood about its expression and function in BC and its prognostic significance. In the present study, we detected the expression level of CD155 in 216 cases of BC by immunohistochemistry (IHC), and we evaluated its relationship with BC patients’ clinical information. We also analyzed the characteristics of CD163, CD8, and CD68 in 216 cases of BC patients through IHC. The results indicated that the CD155 expression level was significantly associated with primary tumor size (x2 = 23.593, P < 0.001), lymph node metastasis (x2 = 15.426, P < 0.001), tumour–node–metastasis (TNM) stage (x2 = 19.693, P < 0.001), Ki-67 (x2 = 9.355, P = 0.002), and CD163/CD8/CD68 expression on statistical analysis. BC patients with high expression of CD155 had poor overall survival rate, on both univariate analysis (Hazard ratio = 2.681, 95% CI = 1.458–4.928, P < 0.001) and multivariate analysis (Hazard ratio = 2.029, 95% CI = 1.059–3.887, P = 0.033). These results suggest an interaction between CD155 expression and tumor-infiltrating lymphocytes (TILs) in BC, and they also suggest that CD155 could be an effective prognostic biomarker for BC.

Intrinsic chemoresistance is the main reason for the failure of human pancreatic ductal adenocarcinoma (PDAC) therapy. To identify the candidate protein, we compared the protein expression profiling of PDAC cells and its distinct surviving cells following primary treatment with gemcitabine (GEM) and 5-fluorouracil (5-FU) by two-dimensional electrophoresis combined with liquid chromatography-mass spectrometry or mass spectrometry. A total of 20 differentially expressed proteins were identified, and annexin A1 (ANXA1) was analyzed for further validation. The functional validation showed that the downregulation of ANXA1 contributes to GEM and 5-FU resistance in PDAC cells through protein kinase C/c-Jun N-terminal kinase/P-glycoprotein signaling pathway. Our findings provide a platform for the further elucidation of the underlying mechanisms of PDAC intrinsic chemoresistance and demonstrated that ANXA1 may be a valid marker for anticancer drug development.

Table S2. Multvariate Cox regression analysis of PTBP3 expression on 5-year overall and disease specific survival of CRC patients. (DOCX 15 kb)

Table S1. Univariate Cox regression analysis of PTBP3 expression and clinicopathologic variables predicting the survival of CRC patients. (DOCX 16 kb)

PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) is a novel cloned gene located at human chromosome 8p23, playing a vital role in maintaining telomeres length and chromosome stability. It has been demonstrated to be involved in tumor genesis and progression in most malignancies. However, some researches showed opposing molecular status of PinX1 gene and its expression patterns in several other types of tumors. The pathogenic mechanism of PinX1 expression in human malignancy is not yet clear. Moreover, emerging evidence suggest that PinX1 (especially its TID domain) might be a potential new target cancer treatment. Therefore, PinX1 may be a new potential diagnostic biomarker and therapeutic target for human cancers, and may play different roles in different human cancers. The functions and the mechanisms of PinX1 in various human cancers remain unclear, suggesting the necessity of further extensive works of its role in tumor genesis and progression.

Circular RNAs (circRNAs) can participate in multiple cancers, including breast cancer. Increasing circRNAs are recognized in various cancers because of the high-throughput sequencing. However, the potential physiological effect of hsa_circ_0136666 in breast cancer progression is unknown. In our study, the biological role of hsa_circ_0136666 in breast cancer development was studied. It was displayed that hsa_circ_0136666 was greatly increased in breast cancer. In addition, overexpression of hsa_circ_0136666 was able to promote Michigan Cancer Foundation-7 (MCF7) and BT474 cell proliferation and triggered cell cycle in G2/M phase. microRNA plays critical role in tumor development and they can act as direct targets of circRNAs. miR-1299 has been implicated as a famous tumor suppressor in many cancers. Here, miR-1299 was predicted as the target of hsa_circ_0136666. Meanwhile, its Upregulation repressed breast cancer proliferation, migration and invasion capacity, which could be reversed by the increase of hsa_circ_0136666. Furthermore, Cyclin-dependent kinase 6 (CDK6) was speculated as the downstream target of miR-1299. In MCF7 and BT474 cells, CDK6 was greatly overexpressed and it was shown that CDK6 contributed a lot to breast cancer progression. Subsequently, it was implied that hsa_circ_0136666 could modulate CDK6 levels positively in vitro. In conclusion, it was revealed that Upregulation of hsa_circ_0136666 promoted breast cancer progression by sponging miR-1299 and targeting CDK6.

Epiregulin (EREG) is a novel family member of EGF-like ligands and have elevated expression in a variety of human cancers. EREG expression promotes tumor progression and metastasis and reduces patient survival. However, the expression of EREG and its prognostic value are not clear in gastric cancer (GC). We assessed EREG mRNA and protein expression in GC tissues from Chinese patients using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining of tissue microarray, and analyzed the correlation between the level of EREG expression and patient clinical characteristics and prognosis. We found that EREG expression was significantly higher in GC tissues than in matched adjacent noncancerous tissues. High EREG protein expression in GC was significantly associated with TNM stage including tumor size, lymph node metastases and distant metastases as well as poor overall survival. These finding demonstrate that EREG is an independent prognostic biomarker for GC.

RNA-binding motif 4 (RBM4) is a multifunctional protein that participates in regulating alternative splicing and mRNA translation. Its reduced expression has been associated with poor overall survival in lung cancer, breast cancer and ovarian cancer. We assessed RBM4 protein expression levels with immunohistochemistry in tissue microarrays containing malignant gastric cancer tissues and benign tissues from 813 patients. We also examined the expression levels of RBM4 mRNA in twenty-five paired gastric cancer samples and adjacent noncancerous tissues. Both RBM4 protein and mRNA expression levels were significantly lower in gastric cancer tissues compared with the adjacent noncancerous tissues. There was a significant association between reduced RBM4 protein expression and differentiation (P P = 0.026), TNM state (P = 0.014) and distant metastasis (P = 0.036). Patients with reduced RBM4 expression (P P

// Bing Wang 1, 2 , Hongmei Yong 3 , Huijun Zhu 4 , Daguang Ni 1 , Sijie Tang 1 , Shu Zhang 4 , Wei Wang 4 , Yan Zhou 2 , Wei Zhao 5 , Guipeng Ding 5 , Jin Zhu 6 , Xiaohua Li 1, 7, 8 , Zhenqing Feng 2, 5, 9, 10 1 Center for Pathology and Laboratory Medicine, Zhangjiagang Ao Yang Hospital, Zhangjiagang, Jiangsu, China 2 Department of Oncology, Zhangjiagang Ao Yang Hospital, Zhangjiagang, Jiangsu, China 3 Department of Oncology, Huai’an Hospital Affiliated of Xuzhou Medical College and Huai’an Second People’s Hospital, Huai’an, Jiangsu, China 4 Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China 5 Department of Pathology, Nanjing Medical University, Nanjing, China 6 Huadong Medical Institute of Biotechniques, Nanjing, China 7 School of Medicine, Jiangsu University, Jiangsu, China 8 The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China 9 Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, China 10 Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China Correspondence to: Xiaohua Li, email: joshua28li@163.com Zhenqing Feng, email: fengzhenqing@njmu.edu.cn Keywords: gastric cancer, amphiregulin, prognosis Received: April 05, 2016 Accepted: September 27, 2016 Published: October 04, 2016 ABSTRACT Gastric cancer (GC) is a global health issue with a high mortality rate. Early diagnosis and tracking of GC is a challenge due to a lack of reliable tools. Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family that activates growth signaling upon binding of EGF receptors. Elevated AREG expression is associated with various pathological conditions, including cancer. Here, we investigated whether increased AREG expression is a disease indicator and/or prognostic biomarker for GC. We used tissue microarray and quantitative real-time polymerase chain reaction to assess AREG expression in clinical tissue specimens at various stages of GC and a conducted bioinformatics analysis to evaluate the value of AREG over-expression as a GC biomarker. We found that both mRNA and protein expression of AREG were increased in the tissues of GC patients when compared to tissues from non-cancer patients or normal tissues. High expression of AREG was also associated with GC clinicopathological characteristics and poor survival. Thus, over-expression of AREG could serve as a novel GC biomarker, and active surveillance of its expression could be a novel approach to GC diagnosis and monitoring.

To evaluate the role of RUNX3 in breast cancer pathogenesis, we examined the RUNX3 expression in breast cancer tissues and analyzed the correlation between RUNX3 expression and clinicopathologic variables and patients survival. We evaluated the RUNX3 expression by immunohistochemistry using a tissue microarray containing 256 specimens of breast cancer patients. We also studied the role of RUNX3 in cell migration and invasion by performing cell migration and invasion assay. Differential expression of metastasis-related genes after RUNX3 restoration was analyzed using the Human Tumor Metastasis PCR Array. The RUNX3 expression was significantly correlated with breast cancer histology grade (P = 0.000), and low RUNX3 expression strongly correlated with worse 5-year overall and disease-specific survival rates (P = 0.000 and P = 0.001, respectively). Furthermore, we found that RUNX3 restoration suppressed breast cancer metastasis by controlling cell migration and invasion capacity. Finally, gene expression profiles of RUNX3-549 and Ctrl-549 cells showed matrix metalloproteinase-2 (MMP-2) was the most significant gene among the 84 metastasis-related genes influenced by RUNX3 reintroduction. Reduced RUNX3 expression is significantly correlated with breast cancer progression and predicts worse survival. RUNX3 regulates breast cancer cell migration and invasion through the MMP-2 pathway.