Type 2 hypersensitivity disorders, including systemic lupus erythematosus, Sjögren's syndrome, Graves' disease, myasthenia gravis, immune thrombocytopenia, autoimmune hemolytic anemia, dermatomyositis, and graft-versus-host disease, are THαß-dominant autoimmune diseases.

The THαß host immunological pathway contributes to the response to infectious particles (viruses and prions). Furthermore, there is increasing evidence for associations between autoimmune diseases, and particularly type 2 hypersensitivity disorders, and the THαß immune response. For example, patients with systemic lupus erythematosus often produce anti-double stranded DNA antibodies and anti-nuclear antibodies and show elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 throughout the disease course. These cytokines and antibody isotypes are associated with the THαß host immunological pathway. Similarly, the type 2 hypersensitivity disorders myasthenia gravis, Graves' disease, graft-versus-host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjögren's syndrome have also been linked to the THαß pathway. Considering the potential associations between these diseases and dysregulated THαß immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferon α/ß could be explored for effective management.

Sushi Domain Containing 2 Dysfunction Contributes to Cancer Progression in Patients with Bladder Cancer.

Bladder cancer is the most prevalent type of cancer in Taiwan, and therefore, enhancing the diagnostic sensitivity of biomarkers for early-stage tumors and identifying therapeutic targets to improve patient survival rates are essential. Although Sushi Domain Containing 2 (SUSD2) dysfunction has been identified in several types of human cancer, its biological role in bladder cancer remains unclear. Analysis of The Cancer Genome Atlas revealed significantly higher expression of SUSD2 mRNA in bladder cancer tissues than in adjacent normal tissues. This elevated expression of SUSD2 significantly correlated with pathological stage (p = 0.029), pN stage (p < 0.001), and pM stage (p = 0.047). Univariate analysis revealed that high SUSD2 expression was associated with decreased overall survival (crude hazard ratio = 1.70, 95% confidence interval = 1.13-2.56, p = 0.01). Multivariate analysis revealed a significant correlation between high SUSD2 expression and poor survival outcomes (adjusted hazard ratio = 1.53, 95% confidence interval = 1.01-2.31, p = 0.043). IHC analysis revealed a significant correlation between elevated SUSD2 protein levels and unfavorable pathological stages (p < 0.001). SUSD2 suppression significantly reduced the proliferation, colony formation, and invasion of bladder cancer cells. In addition, cell cycle analysis revealed that SUSD2 knockdown induced G2/M phase arrestin bladder cancer cells. Tumor Immune Estimation Resource analysis indicated that expression of SUSD2 was significantly associated with macrophage infiltration and M2 macrophage polarization in bladder cancer. In addition, miR-383-5p directly targeted the 3'UTR of SUSD2, with its ectopic expression inhibiting the growth and motility of bladder cancer cells. Our study revealed that miR-383-5p/SUSD2 axis dysfunction may contribute to a poor prognosis for bladder cancer by affecting cell growth, metastasis, and the tumor microenvironment.

Overexpression of malic enzyme is involved in breast cancer growth and is correlated with poor prognosis.

Malic enzyme (ME) genes are key functional metabolic enzymes playing a crucial role in carcinogenesis. However, the detailed effects of ME gene expression on breast cancer progression remain unclear. Here, our results revealed ME1 expression was significantly upregulated in breast cancer, especially in patients with oestrogen receptor/progesterone receptor-negative and human epidermal growth factor receptor 2-positive breast cancer. Furthermore, upregulation of ME1 was significantly associated with more advanced pathological stages (p < 0.001), pT stage (p < 0.001) and tumour grade (p < 0.001). Kaplan-Meier analysis revealed ME1 upregulation was associated with poor disease-specific survival (DSS: p = 0.002) and disease-free survival (DFS: p = 0.003). Multivariate Cox regression analysis revealed ME1 upregulation was significantly correlated with poor DSS (adjusted hazard ratio [AHR] = 1.65; 95% CI: 1.08-2.52; p = 0.021) and DFS (AHR, 1.57; 95% CI: 1.03-2.41; p = 0.038). Stratification analysis indicated ME1 upregulation was significantly associated with poor DSS (p = 0.039) and DFS (p = 0.038) in patients with non-triple-negative breast cancer (TNBC). However, ME1 expression did not affect the DSS of patients with TNBC. Biological function analysis revealed ME1 knockdown could significantly suppress the growth of breast cancer cells and influence its migration ability. Furthermore, the infiltration of immune cells was significantly reduced when they were co-cultured with breast cancer cells with ME1 knockdown. In summary, ME1 plays an oncogenic role in the growth of breast cancer; it may serve as a potential biomarker of progression and constitute a therapeutic target in patients with breast cancer.

Phosphofructokinase Platelet Overexpression Accelerated Colorectal Cancer Cell Growth and Motility.

Background: Glycolysis is a glucose metabolism pathway that generates the high-energy compound adenosine triphosphate, which supports cancer cell growth. Phosphofructokinase platelet (PFKP) plays a crucial role in glycolysis regulation and is involved in human cancer progression. However, the biological function of PFKP remains unclear in colorectal cancer (CRC). Methods: We analyzed the expression levels of PFKF in colon cancer cells and clinical samples using real-time PCR and western blot techniques. To determine the clinical significance of PFKP expression in colorectal cancer (CRC), we analyzed public databases. In addition, we conducted in vitro assays to investigate the effects of PFKP on cell growth, cell cycle, and motility. Results: An analysis by the Cancer Genome Atlas database revealed that PFKP was significantly overexpressed in CRC. We examined the levels of PFKP mRNA and protein, revealing that PFKP expression was significantly increased in CRC. The results of the univariate Cox regression analysis showed that high PFKP expression was linked to worse disease-specific survival (DSS) and overall survival (OS) [DSS: crude hazard ratio (CHR) = 1.84, 95% confidence interval (CI): 1.01-3.36, p = 0.047; OS: CHR=1.91, 95% CI: 1.06-3.43, p = 0.031]. Multivariate Cox regression analysis revealed that high PFKP expression was an independent prognostic biomarker for the DSS and OS of patients with CRC (DSS: adjusted HR = 2.07, 95% CI: 1.13-3.79, p = 0.018; AHR = 2.34, 95% CI: 1.29-4.25, p = 0.005). PFKP knockdown reduced the proliferation, colony formation, and invasion of CRC cells. In addition, the knockdown induced cell cycle arrest at the G0/G1 phase by impairing cell cycle-related protein expression. Conclusion: Overexpression of PFKP contributes to the growth and invasion of CRC by regulating cell cycle progression. PFKP expression can serve as a valuable molecular biomarker for cancer prognosis and a potential therapeutic target for treating CRC.

Synergistic Effect of Metformin and Lansoprazole Against Gastric Cancer through Growth Inhibition.

Cancer has been linked to metabolic disorders and diverse gene mutations. Metformin, which is widely used to treat type 2 diabetes, inhibits the growth of cancer cells in animal models. Here we investigated the effects of metformin on human gastric cancer cell lines. We also investigated the synergistic anticancer effect of metformin and proton pump inhibitors. Lansoprazole, a proton pump inhibitor, is effective for treating gastroesophageal reflux disease. Our results revealed that metformin and lansoprazole can significantly inhibit cancer cell growth in a dose-dependent manner by suppressing cell cycle progression and inducing apoptosis. Low concentrations of metformin and lansoprazole have a synergistic effect on AGS cell growth inhibition. In summary, our findings suggest a new and safe treatment protocol for treating stomach cancers.

Breast Cancer with Increased Drug Resistance, Invasion Ability, and Cancer Stem Cell Properties through Metabolism Reprogramming.

Breast cancer is a heterogeneous disease, and the survival rate of patients with breast cancer strongly depends on their stage and clinicopathological features. Chemoradiation therapy is commonly employed to improve the survivability of patients with advanced breast cancer. However, the treatment process is often accompanied by the development of drug resistance, which eventually leads to treatment failure. Metabolism reprogramming has been recognized as a mechanism of breast cancer resistance. In this study, we established a doxorubicin-resistant MCF-7 (MCF-7-D500) cell line through a series of long-term doxorubicin in vitro treatments. Our data revealed that MCF-7-D500 cells exhibited increased multiple-drug resistance, cancer stemness, and invasiveness compared with parental cells. We analyzed the metabolic profiles of MCF-7 and MCF-7-D500 cells through liquid chromatography−mass spectrometry. We observed significant changes in 25 metabolites, of which, 21 exhibited increased levels (>1.5-fold change and p < 0.05) and 4 exhibited decreased levels (<0.75-fold change and p < 0.05) in MCF-7 cells with doxorubicin resistance. These results suggest the involvement of metabolism reprogramming in the development of drug resistance in breast cancer, especially the activation of glycolysis, the tricarboxylic acid (TCA) cycle, and the hexamine biosynthesis pathway (HBP). Furthermore, most of the enzymes involved in glycolysis, the HBP, and the TCA cycle were upregulated in MCF-7-D500 cells and contributed to the poor prognosis of patients with breast cancer. Our findings provide new insights into the regulation of drug resistance in breast cancer, and these drug resistance-related metabolic pathways can serve as targets for the treatment of chemoresistance in breast cancer.

Cancer as a Dysfunctional Immune Disorder: Pro-Tumor TH1-like Immune Response and Anti-Tumor THαß Immune Response Based on the Complete Updated Framework of Host Immunological Pathways.

Host immunological pathways are delicate to cope with different types of pathogens. In this article, we divide immunological pathways into two groups: Immunoglobulin G-related eradicable immunities and Immunoglobulin A-related tolerable immunities. Once immune cells encounter an antigen, they can become anergic or trigger immune reactions. Immunoglobulin D B cells and γδ T cells are recognizing self-antigens to become anergic. Immunoglobulin M B cells and αß T cells can trigger host immune reactions. Eradicable immune responses can be divided into four groups: TH1/TH2/TH22/THαß (TH-T Helper cell groups). Tolerable immune responses can be divided into four groups: TH1-like/TH9/TH17/TH3. Four groups mean hosts can cope with four types of pathogens. Cancer is related to immune dysfunction. TH1-like immunity is pro-tumor immunity and THαß is anti-tumor immunity. TH1-like immunity is the host tolerable immunity against intracellular micro-organisms. THαß immunity is the host eradicable immunity against viruses. Cancer is also related to clonal anergy by Immunoglobulin D B cells and γδ T cells. Oncolytic viruses are related to the activation of anti-viral THαß immunity. M2 macrophages are related to the tolerable TH1-like immunity, and they are related to metastasis. This review is key to understanding the immune pathogenesis of cancer. We can then develop better therapeutic agents to treat cancer.

Targeted Next-Generation Sequencing-Based Multiple Gene Mutation Profiling of Patients with Rectal Adenocarcinoma Receiving or Not Receiving Neoadjuvant Chemoradiotherapy.

This study investigated whether oncogenic and tumor-suppressive gene mutations are involved in the differential outcomes of patients with rectal carcinoma receiving neoadjuvant chemoradiotherapy (nCRT). Genomic DNA was obtained from formalin-fixed paraffin-embedded (FFPE) specimens of patients with rectal carcinoma who received a complete nCRT course. Gene mutation status was examined in specimens from patients before and after nCRT by using the AmpliSeq platform. Our data revealed that the nonsynonymous p53, APC, KRAS, CDKN2A, and EGFR mutations were observed in 93.1%, 65.5%, 48.6%, and 31% of the patients with rectal adenocarcinoma, respectively. BRAF, FBXW7, PTEN, and SMAD4 mutations were observed in 20.7% of patients with rectal carcinoma. The following 12 gene mutations were observed more frequently in the patients exhibiting a complete response than in those demonstrating a poor response before nCRT: ATM, BRAF, CDKN2A, EGFR, FLT3, GNA11, KDR, KIT, PIK3CA, PTEN, PTPN11, SMAD4, and TP53. In addition, APC, BRAF, FBXW7, KRAS, SMAD4, and TP53 mutations were retained after nCRT. Our results indicate a complex mutational profile in rectal carcinoma, suggesting the involvement of BRAF, SMAD4, and TP53 genetic variants in the outcomes of patients with nCRT.

The emerging role of miRNAs in the pathogenesis of COVID-19: Protective effects of nutraceutical polyphenolic compounds against SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause immunosuppression and cytokine storm, leading to lung damage and death. The clinical efficacy of anti-SARS-CoV-2 drugs in preventing viral entry into host cells and suppressing viral replication remains inadequate. MicroRNAs (miRNAs) are crucial to the immune response to and pathogenesis of coronaviruses, such as SARS-CoV-2. However, the specific roles of miRNAs in the life cycle of SARS-CoV-2 remain unclear. miRNAs can participate in SARS-CoV-2 infection and pathogenesis through at least four possible mechanisms: 1. host cell miRNA expression interfering with SARS-CoV-2 cell entry, 2. SARS-CoV-2-derived RNA transcripts acting as competitive endogenous RNAs (ceRNAs) that may attenuate host cell miRNA expression, 3. host cell miRNA expression modulating SARS-CoV-2 replication, and 4. SARS-CoV-2-encoded miRNAs silencing the expression of host protein-coding genes. SARS-CoV-2-related miRNAs may be used as diagnostic or prognostic biomarkers for predicting outcomes among patients with SARS-CoV-2 infection. Furthermore, accumulating evidence suggests that dietary polyphenolic compounds may protect against SARS-CoV-2 infection by modulating host cell miRNA expression. These findings have major implications for the future diagnosis and treatment of COVID-19.

UBE2C triggers HIF-1α-glycolytic flux in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy in Taiwan. Therefore, refining the diagnostic sensitivity of biomarkers for early-stage tumours and identifying therapeutic targets are critical for improving the survival rate of HNSCC patients. Metabolic reprogramming contributes to cancer development and progression. Metabolic pathways, specifically, play a crucial role in these diverse biological and pathological processes, which include cell proliferation, differentiation, apoptosis and carcinogenesis. Here, we investigated the role and potential prognostic value of the ubiquitin-conjugating enzyme E2 (UBE2) family in HNSCC. Gene expression database analysis followed by tumour comparison with non-tumour tissue showed that UBE2C was upregulated in tumours and was associated with lymph node metastasis in HNSCC patients. Knockdown of UBE2C significantly reduced the invasion/migration abilities of SAS and CAL27 cells. UBE2C modulates glycolysis pathway activation and HIF-1α expression in SAS and CAL27 cells. CoCl2 (HIF-1α inducer) treatment restored the expression of glycolytic enzymes and the migration/invasion abilities of UBE2C knockdown cells. Based on our findings, UBE2C expression mediates HIF-1α activation, increasing glycolysis pathway activation and the invasion/migration abilities of cancer cells. UBE2C may be an independent prognostic factor and a therapeutic target in HNSCC.

Long Noncoding RNA LOC550643 Acts as an Oncogene in the Growth Regulation of Colorectal Cancer Cells.

Long noncoding RNAs play a key role in the progression of colorectal cancer (CRC). However, the role and mechanism of LOC550643 in CRC cell growth and metastasis remain largely unknown. In this study, we assessed the clinical impacts of LOC550643 on CRC through the analysis of The Cancer Genome Atlas database, which revealed the significant upregulation of LOC550643 in CRC. Moreover, the high expression of LOC550643 was associated with poor survival in patients with CRC (p = 0.001). Multivariate Cox regression analysis indicated that LOC550643 overexpression was an independent prognostic factor for shorter overall survival in patients with CRC (adjusted hazard ratio, 1.90; 95% confidence interval, 1.21-3.00; p = 0.006). A biological function analysis revealed that LOC550643 knockdown reduced colon cancer cell growth by hindering cell cycle progression. In addition, LOC550643 knockdown significantly induced cell apoptosis through the inhibition of signaling activity in phosphoinositide 3-kinases. Moreover, LOC550643 knockdown contributed to the inhibition of migration and invasion ability in colon cancer cells. Furthermore, miR-29b-2-5p interacted with the LOC550643 sequence. Ectopic miR-29b-2-5p significantly suppressed colon cancer cell growth and motility and induced cell apoptosis. Our findings suggest that, LOC550643-miR-29b-2-5p axis was determined to participate in the growth and metastasis of colon cancer cells; this could serve as a useful molecular biomarker for cancer diagnosis and as a potential therapeutic target for CRC.

Phytochemically Derived Zingerone Nanoparticles Inhibit Cell Proliferation, Invasion and Metastasis in Human Oral Squamous Cell Carcinoma.

Due to its aggressiveness and high mortality rate, oral cancer still represents a tough challenge for current cancer therapeutics. Similar to other carcinomas, cancerous invasion and metastasis are the most important prognostic factors and the main obstacles to therapy for human oral squamous cell carcinoma (OSCC). Fortunately, with the rise of the nanotechnical era and innovative nanomaterial fabrication, nanomaterials are widely used in biomedicine, cancer therapeutics, and chemoprevention. Recently, phytochemical substances have attracted increasing interest as adjuvants to conventional cancer therapy. The ginger phenolic compound zingerone, a multitarget pharmacological and bioactive phytochemical, possesses potent anti-inflammatory, antioxidant, and anticancer activities. In our previous study, we generated phytochemically derived zingerone nanoparticles (NPs), and documented their superior antitumorigenic effect on human hepatoma cells. In the present study, we further investigated the effects of zingerone NPs on inhibiting the invasiveness and metastasis of human OSCC cell lines. Zingerone NPs elicited significant cytotoxicity in three OSCC cell lines compared to zingerone. Moreover, the lower dose of zingerone NPs (25 µM) markedly inhibited colony formation and colony survival by at least five-fold compared to zingerone treatment. Additionally, zingerone NPs significantly attenuated cell motility and invasiveness. In terms of the signaling mechanism, we determined that the zingerone NP-mediated downregulation of Akt signaling played an important role in the inhibition of cell viability and cell motility. Zingerone NPs inhibited matrix metalloproteinase (MMP) activity, which was highly correlated with the attenuation of cell migration and cell invasion. By further detecting the roles of zingerone NPs in epithelial-mesenchymal transition (EMT), we observed that zingerone NPs substantially altered the levels of EMT-related markers by decreasing the levels of the mesenchymal markers, N-cadherin and vimentin, rather than the epithelial proteins, ZO-1 and E-cadherin, compared with zingerone. In conclusion, as novel and efficient phytochemically derived nanoparticles, zingerone NPs may serve as a potent adjuvant to protect against cell invasion and metastasis, which will provide a beneficial strategy for future applications in chemoprevention and conventional therapeutics in OSCC treatment.

THαß Immunological Pathway as Protective Immune Response against Prion Diseases: An Insight for Prion Infection Therapy.

Prion diseases, including Creutzfeldt-Jakob disease, are mediated by transmissible proteinaceous pathogens. Pathological changes indicative of neuro-degeneration have been observed in the brains of affected patients. Simultaneously, microglial activation, along with the upregulation of pro-inflammatory cytokines, including IL-1 or TNF-α, have also been observed in brain tissue of these patients. Consequently, pro-inflammatory cytokines are thought to be involved in the pathogenesis of these diseases. Accelerated prion infections have been seen in interleukin-10 knockout mice, and type 1 interferons have been found to be protective against these diseases. Since interleukin-10 and type 1 interferons are key mediators of the antiviral THαß immunological pathway, protective host immunity against prion diseases may be regulated via THαß immunity. Currently no effective treatment strategies exist for prion disease; however, drugs that target the regulation of IL-10, IFN-alpha, or IFN-ß, and consequently modulate the THαß immunological pathway, may prove to be effective therapeutic options.

High expression of tight junction protein 1 as a predictive biomarker for bladder cancer grade and staging.

Tight junction proteins 1-3 (TJP1-3) are components of tight junctions that can link transmembrane proteins to the actin cytoskeleton, and their incidence directly correlates to metastasis. However, the role of the TJP family in bladder cancer has not been adequately evaluated. In this study, we evaluated the genetic changes, mRNA and protein expressions of the target genes of the TJP family in bladder cancer patients using online database and immunohistochemistry, respectively. We found that TJP1 was amplified in bladder cancer tissue and that the protein expression levels were significantly associated with age (p = 0.03), grade (p = 0.007), and stage (p = 0.011). We also examined the correlation between TJP1 and other high-frequency mutation genes using TIMER. TJP1 mRNA levels were positively correlated with TTN and RYR3 mRNA levels in bladder cancer tissue. Taken together, TJP1 expression is associated with poor clinical outcomes in patients with bladder cancer and can be a useful predictive biomarker for bladder cancer staging.

Plasma BDNF and Cytokines Correlated with Protein Biomarkers for Bipolar II Disorder.

We have previously identified five candidate proteins (matrix metallopeptidase 9 (MMP9), phenylalanyl-TRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin Type 9 (PCSK9)) as potential biomarkers for bipolar II disorder (BD-II). These candidate proteins have been associated with neuroprotective factors (BDNF) and inflammatory factors (cytokines, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α)). However, the correlations between these proteins with plasma BDNF and inflammatory factors remain unknown. We recruited a total of 185 patients with BD-II and 186 healthy controls. Plasma levels of candidate proteins, BDNF, cytokines (TNF-α, CRP, and interleukin-8 (IL-8)) were assessed from each participant. The correlations between levels of candidate proteins, BDNF, and cytokines were analyzed. In the BD-II group, we found that the level of FARSB was positively correlated with the BDNF level (r = 0.397, p < 0.001) and IL-8 (r = 0.320, p < 0.001). The CA-1 level positively correlated with IL-8 (r = 0.318, p < 0.001). In the control group, we found that the FARSB level positively correlated with the BDNF level (r = 0.648, p < 0.001). The CA-1 level positively correlated with TNF-α (r = 0.231, p = 0.002), while the MMP-9 level positively correlated with the CRP level (r = 0.227, p = 0.002). Our results may help in clarifying the underlying mechanism of these candidate proteins for BD-II.

Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis.

Long noncoding RNAs (lncRNAs) are a group of nonprotein coding transcripts that play a critical role in cancer progression. However, the role of lncRNA in metformin-induced inhibition of cell growth and its biological function in gastric cancer remain largely unknown. In this study, we identified an oncogenic lncRNA, Loc100506691, the expression of which was decreased in gastric cancer cells with metformin treatment. Moreover, Loc100506691 was significantly overexpressed in gastric cancer compared with adjacent normal tissues (p < 0.001), and high Loc100506691 expression was significantly correlated with poor survival of patients with gastric cancer. Additionally, Loc100506691 knockdown could significantly suppress gastric cancer cell growth in vitro, and ectopic Loc100506691 expression accelerated tumor growth in an in vivo mouse model. Analysis of the cell cycle revealed that Loc100506691 knockdown induced cell cycle arrest at the G2/M phase by impairing cell entry from the G2/M to G1 phase. Loc100506691 negatively regulated CHAC1 expression by modulating miR-26a-5p/miR-330-5p expression, and CHAC1 knockdown markedly attenuated Loc100506691 knockdown-induced gastric cancer cell growth and motility suppression. We concluded that anti-proliferative effects of metformin in gastric cancer may be partially caused by suppression of the Loc100506691-miR-26a-5p/miR-330-5p-CHAC1 axis.

LOC550643, a Long Non-coding RNA, Acts as Novel Oncogene in Regulating Breast Cancer Growth and Metastasis.

Metastatic disease is responsible for over 90% of death in patients with breast cancer. Therefore, identifying the molecular mechanisms that regulate metastasis and developing useful therapies are crucial tasks. Long non-coding RNAs (lncRNAs), which are non-coding transcripts with >200 nucleotides, have recently been identified as critical molecules for monitoring cancer progression. This study examined the novel lncRNAs involved in the regulation of tumor progression in breast cancer. This study identified 73 metastasis-related lncRNA candidates from comparison of paired isogenic high and low human metastatic breast cancer cell lines, and their expression levels were verified in clinical tumor samples by using The Cancer Genome Atlas. Among the cell lines, a novel lncRNA, LOC550643, was highly expressed in breast cancer cells. Furthermore, the high expression of LOC550643 was significantly correlated with the poor prognosis of breast cancer patients, especially those with triple-negative breast cancer. Knockdown of LOC550643 inhibited cell proliferation of breast cancer cells by blocking cell cycle progression at S phase. LOC550643 promoted important in vitro metastatic traits such as cell migration and invasion. Furthermore, LOC550643 could inhibit miR-125b-2-3p expression to promote breast cancer cell growth and invasiveness. In addition, by using a xenograft mouse model, we demonstrated that depletion of LOC550643 suppressed the lung metastatic potential of breast cancer cells. Overall, our study shows that LOC550643 plays an important role in breast cancer cell metastasis and growth, and LOC550643 could be a potential diagnosis biomarker and therapeutic target for breast cancer.

Circulating miRNAs Act as Diagnostic Biomarkers for Bladder Cancer in Urine.

MicroRNAs (miRNAs) can be secreted into body fluids and have thus been reported as a new type of cancer biomarker. This study aimed to determine whether urinary miRNAs act as noninvasive biomarkers for diagnosing bladder cancer. Small RNA profiles from urine were generated for 10 patients with bladder cancer and 10 healthy controls by using next-generation sequencing. We identified 50 urinary miRNAs that were differentially expressed in bladder cancer compared with controls, comprising 44 upregulated and six downregulated miRNAs. Pathway enrichment analysis revealed that the biological role of these differentially expressed miRNAs might be involved in cancer-associated signaling pathways. Further analysis of the public database revealed that let-7b-5p, miR-149-5p, miR-146a-5p, miR-193a-5p, and miR-423-5p were significantly increased in bladder cancer compared with corresponding adjacent normal tissues. Furthermore, high miR-149-5p and miR-193a-5p expression was significantly correlated with poor overall survival in patients with bladder cancer. The qRT-PCR approach revealed that the expression levels of let-7b-5p, miR-149-5p, miR-146a-5p and miR-423-5p were significantly increased in the urine of patients with bladder cancer compared with those of controls. Although our results indicated that urinary miRNAs are promising biomarkers for diagnosing bladder cancer, this must be validated in larger cohorts in the future.

Prognostic Influence of Cytoplasmic/Nuclear Hepatoma-derived Growth Factor in Head and Neck Cancer.

BACKGROUND/AIM: We investigated the prognostic influence of both hepatoma-derived growth factor (HDGF) and p53 expression in head and neck cancer. MATERIALS AND METHODS: HDGF and p53 immunostaining was scored based on staining intensities and percentage of tumor cells stained using tissue microarray composed of total 102 head and neck cancer samples. RESULTS: Over-expression of HDGF and p53 was observed in cancer compared with adjacent normal tissues (p<0.001). In multivariate analyses, tumors with higher nuclear and cytoplasmic HDGF staining scores (p=0.019), and tumors with cN1-cN2 (compared with cN0) (p=0.014), were associated with worse overall survival. CONCLUSION: The increased expression of HDGF and p53 in the tumor compared with adjacent normal tissues could be a risk factor for tumorigenesis. Increased nuclear and cytoplasmic expression of HDGF, and cN staging correlated with overall survival and negatively influenced prognosis in head and neck cancer.