RESUMEN
The vital functions of long noncoding (lnc)RNAs have been verified in gastric carcinoma (GC). However, as a novel cancerrelated lncRNA, the influence of leukemia inhibitory factor receptor antisense RNA 1 (LIFRAS1) in GC cell biological behaviors remains unreported. The present study explored the biological effects of lncRNA LIFRAS1 on GC progression. Reverse transcriptionquantitative PCR was performed to examine lncRNA LIFRAS1 expression in GC tissues and cells. Cell Counting Kit8, 5ethynyl2'deoxyuridine incorporation, cell wound healing and Transwell invasion assays were used to assess the functions of lncRNA LIFRAS1 in GC cell proliferation, migration and invasion. Additionally, associations among lncRNA LIFRAS1, microRNA (miR)4698 and microtubuleassociated tumor suppressor 1 (MTUS1) were investigated via bioinformatics software and a luciferase reporter system. In addition, western blotting was used to examine the expression of MEK and ERK. Decreased lncRNA LIFRAS1 expression was observed in GC tissues and cells. Upregulated lncRNA LIFRAS1 inhibited GC cell proliferation, migration and invasion. Upregulated miR4698 and downregulated MTUS1 were identified in GC tissues and cells. The inhibitory interaction between lncRNA LIFRAS1 and miR4698 was confirmed. Additionally, MTUS1 was predicted as a target gene of miR4698 positively regulated by lncRNA LIFRAS1. The MEK/ERK pathway was inhibited by lncRNA LIFRAS1 via regulating MTUS1. These findings revealed the inhibitory functions of lncRNA LIFRAS1 in GC cell proliferation, migration and invasion. The process was mediated via miR4698, MTUS1 and the MEK/ERK pathway.
Asunto(s)
Movimiento Celular , Proliferación Celular , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , ARN Neoplásico/metabolismo , Neoplasias Gástricas/metabolismo , Línea Celular Tumoral , Humanos , MicroARNs/genética , Invasividad Neoplásica , ARN Largo no Codificante/genética , ARN Neoplásico/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologíaRESUMEN
PURPOSE: This study aimed to investigate the regulatory effects and mechanisms of long non-coding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on gastric cancer (GC) cells. METHODS: The expression of MALAT1 was detected in GC tissues and two GC cell lines (SGC-7901 and BGC-823). MALAT1 was overexpressed and silenced in GC cells by the transfection of pcDNA-MALAT1 and siRNA-MALAT1, respectively. The proliferation and apoptosis of transfected cells, as well as the tumor volume and weight in mice injected with transfected cells were determined. After identifying the interaction between microRNA-22-3p (miR-22-3p) and MALAT1/epidermal growth factor receptor 3 (ErbB3), the effects of miR-22-3p/ErbB3 silencing on the proliferation and apoptosis of GC cells were evaluated. RESULTS: MALAT1 was significantly upregulated in GC tissues and cells and negatively associated with the survival of GC patients. Overexpression of MALAT1 significantly promoted the proliferation and inhibited the apoptosis of SGC-7901 cells, while silencing of MALAT1 exerts contrary effects on BGC-823 cells. Silencing of MALAT1 also significantly inhibited the tumor growth in mice. In addition, MALAT1 negatively regulated its target miR-22-3p. Silencing of miR-22-3p reversed the anti-tumor effects of MALAT1 silencing on GC cells. MiR-22-3p negatively regulated its target ErbB3. Silencing of ErbB3 reversed the tumor-promoting effects of miR-22-3p silencing on GC cells. CONCLUSION: Silencing of MALAT1 inhibited the proliferation and promoted the apoptosis of GC cells through upregulating miR-22-3p and downregulating ErbB3.
RESUMEN
OBJECTIVE: To observe the inhibitive effect on invasive growth and metastasis of Echinococcus multilocularis by exogenous anti-osteopontin (OPN) antibody. METHODS: 180 gerbils were infected with 20% E. multilocularis suspension (approximately 400 protoscoleces in 0.1 ml per gerbil) through abdominal opening injection in liver, and then divided into model group, experiment group and control group. Experiment group and control group each with 60 gerbils were injected via the tail vein with 0.15 ml of anti-OPN antibody (1:32) and rabbit serum, respectively. All gerbils in the two groups received injections, with 2-day interval for the first seven injections, and then at 7-day interval for the remaining injections. Model group were without any treatment. The three groups were subdivided into six groups each with 10 gerbils. The gerbils from each group were sacrificed on day 1, 20, 40, 60, 80, and 100 after infection, respectively. Hepatic echinococcus cyst and metastasis tissue were observed. The expression of OPN was measured by immunohistochemistry staining (SP method). Serum samples were collected at 100 d post-infection, and the content of OPN in sera was measured by ELISA. RESULTS: There were no significant difference in cyst weight and metastatic rate of thoracic lymph node among the three groups at 1, 20, 40, 60, and 80d post-infection (P > 0.05), while at 100 d postinfection, cyst weight and metastatic rate of thoracic lymph node in experiment group [(7.28 +/- 0.38) g, 20%] were lower than that of control group [(9.70 +/- 0.61) g, 70%] and model group [(932 +/- 0.73) g, 70%] (P < ). Expression of OPN was found at different levels in echinococcus cysts. OPN was located in the cytoplasm, and mainly distributed in the germinal layer. The OPN positive expression levels were not significantly different between experiment group and other groups on day 1, 20, 40, 60, and 80 afer infection ( >0 . 05). At 100d post-infection, OPN positive expression rate and serum OPN content in experimental group [20% and (30.90 +/- 2.25) ng/.l micro respectively] was lower than that of control group [80% and (41.03.2 +/- 76) nWng/micro and model group [80% and (42.39 +/- 2.85) nWng/micro (PdL < 0.). CONCLUSION: Anti-osteopontin antibody can reduce OPN concentration in hepatic echinococcus cyst and serum, and inhibit the invasive growth and metastasis of E. multilocularis.