RESUMO
Colorectal cancer (CRC) is the third most common type of cancer; however, the molecular mechanisms underlying colorectal tumor metastasis and growth remain elusive. Recently, accumulating evidence has indicated that long noncoding RNAs (lncRNAs) play a critical role in CRC progression and metastasis; however, the biological role and clinical significance of lncRNA 00152 (lnc00152) in CRC remains largely unknown. Thus, in this study, lnc00152 expression was measured in 80 human CRC tissue samples, 40 noncancerous tissue samples, and 3 CRC cell lines (SW480, SW620 and LoVo) using RTqPCR. We examined the effects of lnc00152 on CRC cells following transfection with lnc00152 overexpression plasmid or respective siRNA in vitro and in vivo. Luciferase assays revealed the mechanism driving competitive endogenous RNA (ceRNA). We identified that lnc00152 was aberrantly overexpressed in colorectal tumors and cancer cells and that lnc00152 was modulated by miRNA206. lnc00152 overexpression enhanced the proliferative and invasive ability of CRC cells in vitro, promoted tumor growth in vivo, and was associated with the shorter overall survival of patients with CRC. In addition, lnc00152 overexpression promoted epithelial-mesenchymal transition (EMT) and increased neuropilin1 (NRP1) expression in the CRC cells. By contrast, lnc00152 silencing exerted a counteractive effect. Collectively, these findings demonstrate the critical role of lnc00152 in tumor growth and progression in CRC, and identify a novel therapeutic target associated with CRC development and progression.
Assuntos
Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neuropilina-1/genética , RNA Longo não Codificante/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Mutagênese Sítio-Dirigida , Invasividade Neoplásica/genética , Neuropilina-1/metabolismo , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To study the effect of Trichinella spiralis (T.spiralis) infection on the expression and distribution of colonic epithelial E-cadherin in mice and its mechanism. METHODS: BALB/c mice and STAT6-/- mice were infected with T.spiralis, and mice without infection were used as control. Seven days later, the horseradish peroxidase (HRP) was infused by rectal enema. Serum HRP was detected in the subsequent 0, 60 and 120 minutes. Then the mice were sacrificed and colon was taken out. The distribution of E-cadherin in colon was detected by immunofluorescence staining, and the expression of E-cadherin was detected by Western blot. The expression of interleukin-4 (IL-4) in mesenteric lymph nodes was detected by ELISA. RESULTS: Serum HRP level in infected BALB/c mice was significantly higher than that in control mice (P<0.05), while it was not significantly different between infected STAT6-/- mice and controls (P>0.05). In infected BALB/c mice, E-cadherin located in cytoplasm of colonic epithelial cells, while in controls, it located in cellular membrane. E-cadherin expression down-regulated significantly in infected BALB/c mice as compared to controls. E-cadherin expression and distribution did not change obviously in infected STAT6-/- and control mice. IL-4 level in mesenteric lymph nodes of infected BALB/c mice [(193.0±12.5) µg/L] was significantly higher as compared to control BALB/c and infected STAT6-/- mice [(21.0±2.3) µg/L and (15.0±3.1) µg/L, all P<0.05]. CONCLUSION: T.spiralis infection can increase colonic epithelial permeability of mice, which may be associated with induction of Th2 cytokine secretion.