RESUMO
Long non-coding RNAs (lncRNAs) have been revealed to harbor open reading frames (ORFs) that can be translated into small peptides. The peptides may participate in the pathogenesis of colorectal cancer (CRC). Herein, we investigated the role of a lncRNA BVES-AS1-encoded peptide in colorectal tumorigenesis. Through bioinformatic analysis, lncRNA BVES-AS1 was predicted to have encoding potential and to be associated with poor prognosis of patients with CRC. In CRC cells, BVES-AS1 was validated to encode a 50-aa-length micro-peptide, named BVES-AS1-201-50aa, through a western blotting method. BVES-AS1-201-50aa enhanced cell viability and promoted the migratory and invasive capacities of HCT116 and SW480 CRC cells in vitro, validated via CCK-8 assay and transwell assay, respectively. Immunofluorescence assay showed that BVES-AS1-201-50aa increased the expression of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase 9 (MMP9) in CRC cells. We further verified that BVES-AS1-201-50aa targeted and activated the Src/mTOR signaling pathway in CRC cells by co-immunoprecipitation (Co-IP) experiment, qualitative proteomic analysis, and western blotting. Our findings demonstrated that BVES-AS1 could encode a micro-peptide, which promoted CRC cell viability, migration, and invasion in vitro. Our current work broadens the diversity and breadth of lncRNAs in human carcinogenesis.
Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Proteômica , Proliferação de Células/genética , Movimento Celular/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas Musculares/metabolismo , Moléculas de Adesão Celular/metabolismoRESUMO
Aim Furowanin A (Fur A) is a flavonoid isolated from Millettia pachycarpa Benth. Studies show its potent anti-neoplastic effects against leukemia cells. The aim of the present study was to determine the potential therapeutic effect of Fur A against colorectal cancer (CRC), and elucidate the underlying mechanism. MATERIAL AND METHODS: Cell Counting Kit-8 (CCK-8) assay was used to determine cell, and TUNEL and Annexin-V/PI staining was used to detect apoptosis and the cell cycle distribution. The expression levels of specific proteins in the CRC cells were analyzed by Western blotting. A xenograft model was also established to evaluate the therapeutic effect of Fur A in vivo. KEY FINDINGS: Fur A suppressed proliferation, blocked cell cycle progression, induced apoptosis and promoted autophagy in CRC cells. Interestingly, Fur A-induced autophagy functioned not only as a survival mechanism against apoptosis but also intensified the cell cycle arrest in CRC cells. In addition, Fur A mediated its effects via the inactivation of the STAT3/Mcl-1 axis. SIGNIFICANCE: Fur A is a promising drug candidate for the treatment and prevention of CRC.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Isoflavonas/farmacologia , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The present study investigated the expression of miR-21 in MGC803 gastric cancer cells and its effects on Bcl-2 expression and cell proliferation, apoptosis, and invasion. In total 50 patients were recruited with gastric cancer who were admitted to the Henan Province People's Hospital. The samples of gastric cancer and the adjacent normal tissues were collected after surgery. We found that mRNA levels of miR-21 and Bcl-2 were significantly elevated in tumor tissues compared to control tissue. The expression of Bcl-2 protein was also elevated in cancerous tissue. This high expression of Bcl-2 was associated with clinical stage, lymph node metastasis, and tumor differentiation degree. Inhibition of miR-21 reduced the levels of miR-21 and Bcl-2 in MGC803 cells, and lowered cell proliferation and invasiveness. These results indicate that miR-21 and Bcl-2 may participate in the occurrence and development of gastric adenocarcinoma, suggesting their potential role as biomarkers and therapeutic targets.
RESUMO
The effects of laparoscopic radical gastrectomy were observed, and changes in immune function and inflammatory factors of gastric cancer patients were examined. In total, 236 cases of laparoscopic radical gastrectomy were selected between March 2014 and October 2015 and divided into the control and experimental groups. The control group was treated using open radical gastrectomy, while laparoscopic radical gastrectomy was used in the experimental group. Treatment effects, immune function and inflammatory factor in the two groups were compared. Compared to the open radical gastrectomy group, surgery time in the laparoscopic radical gastrectomy group was longer, while blood loss during operation, time of exsufflation through anus after operation, duration of acesodyne use, length of stay and incidence of complications were lower, and the differences were statistically significant (P<0.05). As for the amount of lymph node dissection, differences between the two groups were of no statistical significance (P>0.05). CD3+, CD4+ and CD4+/CD8+ cell ratios in the two groups 1 and 7 days after surgery were obviously lower than those before surgery (P<0.05) while CD8+ was higher. In addition, compared with the open radical gastrectomy group, CD3+, CD4+, CD4+/CD8+ cell ratios in the laparoscopic radical gastrectomy group increased while CD8 was lower, and differences were statistically significant (P<0.05). Differences of interleukin (IL)-6, tumor necrosis factor (TNF) and CRP between the two groups 1 day before surgery were of no statistical significance (P>0.05). One day after surgery, IL-6, TNF and CRP in the two groups increased (P<0.05) and the values in the open radical gastrectomy group were higher (P<0.05). Differences in IL-6 between the two groups 7 days after surgery were of no statistical significance (P>0.05). However, for CRP and TNF, the two values gradually decreased and the differences between the groups were of statistical significance (P<0.05). In conclusion, laparoscopic radical gastrectomy has better treatment effects, lower inflammatory response, less impact on the immune system and fewer complications, which is worth clinical consideration.