ABSTRACT
Colon cancer (COAD) is a prevalent gastrointestinal tumor, composed of a few cancer stem cells (CSCs). High expression of RNF183 drives colorectal cancer metastasis, but its role in COAD cell stemness is still unclear. Bioinformatics analyzed expression and enriched pathway of RNF183 in COAD tissue. IHC analyzed RNF183 protein expression in tumor tissue. CD133 + CD44+ CSCs were sorted by flow cytometry, and RNF183 expression in COAD cells or CSCs was detected by qPCR, western blot and immunofluorescence. CCK-8 assay assessed cell viability, and sphere formation assay tested cell sphere-forming ability. Western blot measured protein expression of stem cell markers. qPCR assayed expression of fatty acid oxidation genes. The ability of fatty acid oxidation was analyzed by detecting fatty acid metabolism. RNF183 was highly expressed in COAD and CD133 + CD44+ CSCs, and was enriched in fatty acid metabolism pathway. RNF183 expression was positively correlated with enzymes involved in fatty acid oxidation. RNF183 could promote COAD stemness and fatty acid oxidation. Rescue experiments showed that Orlistat (a fatty acid oxidation inhibitor) reversed stimulative impact of RNF183 overexpression on COAD stemness. RNF183 promoted COAD stemness by affecting fatty acid oxidation, which may be a new therapeutic target for inhibiting COAD development.
Subject(s)
Colonic Neoplasms , Humans , Cell Line, Tumor , Cell Proliferation , Colonic Neoplasms/pathology , Cell Movement , Fatty Acids/metabolism , Neoplastic Stem Cells/pathology , Gene Expression Regulation, Neoplastic , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
Accumulating research implicated that circular RNAs exhibited significant roles in cancer development. Nonetheless, the role regarding circPTPN22 in pancreatic cancer remains unclear. Expression of circPTPN22 in pancreatic cancer cell lines and normal cells was determined with quantitative real-time PCR (qRT-PCR). Cell counting kit-8 assay and colony formation assay were used to measure the proliferation of pancreatic cancer cells. RNA immunoprecipitation and Western blot were employed for investigation the binding between circPTPN22 and STAT3. circPTPN22 expression was highly upregulated in pancreatic cancer tissues and cell lines. Knockdown of circPTPN22 inhibited cell proliferation and attenuates pancreatic cancer immune microenvironment. Furthermore, STAT3 acetylation was involved in these effects. circPTPN22 promoted STAT3 acetylation via inhibiting STAT3/SIRT1 interaction. circPTPN22 attenuates pancreatic cancer immune microenvironment by promoting STAT3 acetylation via inhibiting STAT3/SIRT1 interaction.
Subject(s)
Pancreatic Neoplasms , Sirtuin 1 , Humans , Sirtuin 1/genetics , Sirtuin 1/metabolism , Acetylation , RNA , Cell Proliferation/genetics , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Cell Line, Tumor , Tumor Microenvironment/genetics , Pancreatic NeoplasmsABSTRACT
OBJECTIVE: Identification of reliable biomarkers for the diagnosis and prognosis of gastric cancer (GC) is very important for achieving early cancer detection and improving clinical outcomes. The aim of the present study was to explore the clinical significance of serum exosomal miR-134 in GC. METHODS: A total of 133 GC cases were enrolled in this study, and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was carried out to measure the relative serum exosomal miR-134 expression level. The association between serum exosomal miR-134 expression and clinicopathological characteristics was investigated. RESULTS: Our results showed that serum exosomal miR-134 expression was significantly lower in GC patients than in controls. In addition, serum exosomal miR-134 discriminated GC cases from healthy controls with high accuracy. Moreover, reduced serum exosomal miR-134 expression was closely associated with aggressive clinical variables including TNM stage, lymph node metastasis and invasion depth. Furthermore, Kaplan-Meier analysis revealed that GC patients with low serum exosomal miR-134 expression tended to have shorter overall survival and relapse free survival. In multivariate analysis, serum exosomal miR-134 was an independent prognostic marker for GC. CONCLUSION: In conclusion, serum exosomal miR-134 might serve as a promising diagnostic and prognostic biomarker for GC.
Subject(s)
MicroRNAs , Stomach Neoplasms , Biomarkers, Tumor/genetics , Humans , MicroRNAs/metabolism , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Stomach Neoplasms/diagnosis , Stomach Neoplasms/geneticsABSTRACT
The aim of the present study was to investigate the expression of fibulin-2 and ß-catenin in gastric cancer tissues and the association to mutual regulation. Forty-nine cases of gastric cancer specimens obtained via surgical resection in the Pathology Department of Heping Hospital Affiliated to Changzhi Medical College from March 2013 to August 2017 were collected. The expression levels of fibulin-2 and ß-catenin in 49 cases of gastric cancer and para-carcinoma tissues were detected via quantitative polymerase chain reaction and immunohistochemistry. The correlation of expression of fibulin-2 and ß-catenin proteins in gastric cancer was detected via Spearman's analysis. The correlation of fibulin-2 and ß-catenin protein expression with clinicopathological indexes of patients was also analyzed. Moreover, the fibulin-2 overexpression plasmid was constructed and transfected into human gastric cancer AGS and SGC-790 cell lines, so as to observe changes in ß-catenin and its downstream indexes. Fibulin-2 messenger ribonucleic acid (mRNA) level in gastric cancer tissues was significantly lower than that in para-carcinoma tissues, while ß-catenin mRNA level was significantly increased (P<0.05). The positive rate of fibulin-2 protein was 73.47% (36/49) in gastric cancer tissues and 16.33% (8/49) in para-carcinoma tissues, while that of ß-catenin was 77.55% (38/49) in gastric cancer tissues and 28.57% (14/49) in para-carcinoma tissues, indicating that fibulin-2 protein is significantly deleted in gastric cancer tissues, and ß-catenin protein is significantly upregulated (P<0.001). Fibulin-2 and ß-catenin had a negative correlation (r=-0.361, P=0.003), but was closely correlated with the tumor size and lymph node metastasis (P<0.05). After overexpression of fibulin-2, expression of ß-catenin, cyclin D1 and c-Myc protein was obviously downregulated (P<0.05). The tumor suppressor gene, fibulin-2, is significantly deleted in gastric cancer tissues, while ß-catenin is remarkably enriched. Overexpression of fibulin-2 can inhibit the development of gastric cancer by downregulating ß-catenin.
ABSTRACT
BACKGROUND MicroRNAs (miRNAs) have been widely recognized as essential regulators in human cancers, including colorectal cancer (CRC). Whether miR-769 is implicated in CRC progression remains elusive. The present study aimed to determine the function of miR-769 in CRC. MATERIAL AND METHODS MiR-769 expression in CRC tissues and adjacent normal tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Kaplan-Meier curve analysis was utilized to determine the association between miR-769 expression and prognosis in CRC patients. The effects of miR-769 overexpression on CRC cell proliferation, cell cycle and invasion were analyzed using Cell Counting Kit-8 (CCK8), fluorescence activated cell sorting (FACS), and Transwell assays. Western blot was utilized to assess the effect of miR-769 on HEY1 expression. RESULTS MiR-769 expression was decreased in CRC tissues. MiR-769 level was negatively correlated with the prognosis of CRC patients. Additionally, miR-769 overexpression remarkably inhibited cell proliferation, arrested CRC cells in G0 stage, and reduced cellular invasion. As to the mechanism, HEY1 was a direct target of miR-769; HEY1 level was inversely correlated with that of miR-769 in CRC tissues. Finally, overexpression of HEY1 reversed the effects of miR-769 on cell proliferation and invasion in CRC. CONCLUSIONS Our findings demonstrated that miR-769 suppressed the proliferation and invasion of CRC cells through targeting HEY1, which implied that miR-769 might be a novel therapeutic target for CRC treatment.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Cycle Proteins/metabolism , Colorectal Neoplasms/metabolism , MicroRNAs/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Cell Cycle/physiology , Cell Cycle Proteins/genetics , Cell Division/physiology , Cell Line, Tumor , Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , HCT116 Cells , HT29 Cells , Humans , Kaplan-Meier Estimate , MicroRNAs/genetics , Neoplasm Invasiveness/genetics , PrognosisABSTRACT
LINC00473 is an intergenic long noncoding RNA (lncRNA) and has been suggested to be dysregulated in several human cancers. However, the clinical value and biological function of LINC00473 in gastric cancer (GC) was still unknown. In our results, LINC00473 expression was increased in GC tissue samples and GC cell lines compared with paired adjacent normal stomach tissue samples and normal gastric epithelial cell line, respectively. High-expression of LINC00473 was correlated with poor histological type, advanced clinical stage, more lymph node metastasis and present distant metastasis. The results of Kaplan-Meier analysis and TCGA database similarly suggested that GC patients with LINC00473 high-expression had poorer prognosis than GC patients with LINC00473 low-expression. Furthermore, multivariate analysis showed that LINC00473 high-expression served as independent unfavorable prognostic factor for overall survival in GC patients. The study in vitro indicated that silencing of LINC00473 had no effect on GC cell viability, but inhibited GC cell migration and invasion through modulating MMP2 and MMP9 expression. In conclusion, LINC00473 is associated with the malignant status and prognosis in GC cases, and functions as an oncogenic lncRNA to regulate GC cell migration and invasion.
Subject(s)
Cell Movement/genetics , RNA, Long Noncoding/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Cadherins/metabolism , Cell Line, Tumor , Down-Regulation/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Prognosis , Proportional Hazards Models , RNA, Long Noncoding/genetics , Vimentin/metabolismABSTRACT
The aim of the present study was to compare the effects of bone marrow-derived mesenchymal stem cells (BMSCs) transplanted via the portal vein or tail vein on liver injury in rats with liver cirrhosis. BMSCs were isolated from rat bone marrow and labeled with green fluorescent protein (GFP). Then, the labeled BMSCs were injected into rats with liver injury via the portal vein or tail vein. Two weeks after transplantation, three rats in each group were sacrificed to test the distribution of GFP in the liver and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin. Six weeks later, the remaining rats were sacrificed, and serum ALT, AST, albumin, hyaluronic acid (HA), laminin (LN) and procollagen type III (PC-III) levels were measured. The expression of albumin in the liver was analyzed by immunohistochemistry. Two weeks after BMSC transplantation, GFP-positive cells were detected in the livers of rats with BMSCs transplanted via the portal vein and tail vein. Compared with pre-transplantation levels, the ALT levels of the groups with BMSC transplantation via the portal vein and tail vein were significantly decreased after two and six weeks of BMSC transplantation (P<0.05), whereas the AST and albumin levels were not significantly different at two weeks after BMSC transplantation in the two groups (all P>0.05). However, the AST and albumin levels were significantly reduced at six weeks after BMSC transplantation (all P<0.05). At six weeks after BMSC transplantation, the serum HA, LN and PC-III levels in rats transplanted with BMSCs via the portal vein or tail vein had decreased significantly (all P<0.05), as compared with the levels prior to BMSC transplantation. BMSCs transplanted via the portal vein and tail vein achieved similar improvements in liver function in rats with liver cirrhosis, which suggests that peripheral venous administration is a convenient and effective route for BMSC transplantation.
ABSTRACT
Esophageal cancer is a common malignancy, for which surgery is the most effective treatment. Compared with traditional surgery, video-assisted thoracoscopic and laparoscopy minimally invasive surgery enables less trauma, better visibility, reduced bleeding and postoperative pain, and lower incidence of surgical complications through a minimally invasive, safe, and highly cost-effective approach in favor of early rehabilitation after surgery. Therefore, the promotion and application of this surgical approach will undoubtedly benefit the majority of patients with esophageal cancer. We have performed video-assisted thoracoscopic and laparoscopy minimally invasive surgery for more than 150 patients in our hospital to date, and have carried out a series of studies in this regard. As the video shows, this approach is safe and reliable with minimal injury and bleeding.
ABSTRACT
In 1910, laparoscopy was applied in the cautery division of pleural adhesions for the first time for cavity pulmonary tuberculosis patients, which was the beginning of thoracoscopic surgery. After 1945, with the introduction of antituberculosis drugs like streptomycin and isoniazid, thoracoscopic surgery faded out. In the 1980s, success of video-assisted laparoscopic surgery in cholecystectomy created a basis for thoracoscopic surgery (VATS). In 1986, micro endoscopic technique was applied in thoracoscopy. In the 1990s, VATS was used in diagnosis and treatment of many kinds of diseases, such as palmar hyperhidrosis, pleural diseases, lung diseases, esophageal diseases and cardiac surgery. With the development of VATS, its application range became wider and wider. In some medical centers, VATS represents 80% of thoracic surgeries.