Here we confirmed that metastasis-associated in colon cancer 1 (MACC1) and β-catenin expression were higher in colorectal cancer (CRC) cells and tissues than those in normal colonic epithelial cell line and adjacent non-tumour colorectal mucosa (ANM) tissues, respectively. MACC1 expression was significantly related to histological differentiation (p<0.001), UICC stage (p=0.029), T classification (p=0.017), and N classification (p=0.023). Cox regression analysis demonstrated that high MACC1/abnormal β-catenin expression was the strongest independent prognostic indicator for reduced overall survival in CRC patients. Significant positive correlation between MACC1 expression and abnormal β-catenin expression was found in CRC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, colony formation, and tumorigenesis, both in vitro and in vivo, but induced apoptosis in CRC cells. Further MACC1 over-expression increased Met, β-catenin, and its downstream genes including c-Myc, cyclin D1, and MMP9 expression, and its upstream gene phos-GSK3β (Ser9) expression. In addition, MACC1 increased vimentin and suppressed E-cadherin in HCT116 cells. Silencing of MACC1 reversed all these changes. Our results firstly suggest that MACC1 plays an important role in carcinogenesis and progression of CRC through β-catenin signaling pathway and mesenchymal-epithelial transition.

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The present study was aimed at investigating the expression of metastasis-associated in colon cancer 1 (MACC1) in nasopharyngeal carcinoma (NPC), its relationship with β-catenin, Met expression and the clinicopathological features of NPC, and its roles in carcinogenesis of NPC. Our results showed that MACC1 expression was higher in NPC cells and tissues than that in normal nasopharyngeal cells and chronic inflammation of the nasopharynx tissues, respectively. MACC1 expression was closely related to the clinical stage (p = 0.005) and the N classification (p<0.05) of NPC. Significant correlations between MACC1 expression and Met expression (p = 0.003), MACC1 expression and β-catenin abnormal expression (p = 0.033) were found in NPC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, and colony formation, but induced apoptosis in NPC cells compared with the control group. Furthermore, MACC1 down-regulation inhibited phosphorylated-Akt (Ser473) and β-catenin expression in NPC cells, but phosphorylated-Erk1/2 expression was not altered. Further study showed that phosphotidylinsitol-3-kinase inhibitor downregulated β-catenin and Met expression in NPC cells. There was a significant relationship between MACC1 expression and phosphorylated-Akt expression (p = 0.03), β-catenin abnormal expression and phosphorylated-Akt expression (p = 0.012) in NPC tissue, respectively. In addition, Epstein Barr virus-encoded oncogene latent membrane protein 1 upregulated MACC1 expression in NPC cells. Our results firstly suggest that MACC1 plays an important role in carcinogenesis of NPC through Akt/β-catenin signaling pathway. Targeting MACC1 may be a novel therapeutic strategy for NPC.

Up to accomplishment of this study, the role of long non-coding RNAs (lncRNAs) in breast cancer has been investigated in several researches. Nevertheless, its association with the chemosensitivity of cancer was little known. Therefore, this study is focused on lncRNA GAS5 and its influence in the chemosensitivity of triple-negative breast cancer (TNBC).Expression of GAS5 in TNBC tissues and cells was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and its methylation was evaluated using methylationspecific polymerase chain reaction (MSP). Moreover, in order to define the contributory role of GAS5 in TNBC, GAS5 expression, proliferation, and apoptosis of TNBC cells were detected by a series of experiment. Finally, the effects of GAS5 in vivo were investigated by measuring tumor formation in nude mice.GAS5 was poorly expressed in TNBC tissues and cells, which could regulate the progression of TNBC. The methylation of CpG island in the promoter region of GAS5 in MDA-MB-231 and MDA-MB-468 cells was decreased, while GAS5 expression in cells was increased. Overexpressed GAS5 reduced the inhibitory concentration (IC50) value and the cell proliferation of TNBC, and promoted their apoptosis, so as to delay the progression of TNBC.Our study provides evidence that up-regulated GAS5 suppressed the progression of TNBC and promoted chemosensitivity and apoptosis of TNBC cells. Thus, GAS5 may be a potential candidate for the treatment of TNBC.

Long noncoding RNAs (lncRNAs) are emerging as a class of important biological regulators. lncRNAs participate in diverse biological functions and disease processes, especially those leading to tumorigenesis. In this study, we investigate the role of linc00261 in the pathogenesis of breast cancer. Methods: linc00261 and NME1 expression levels were determined in breast cancer tissue and adjacent normal tissue using qRT-PCR. Cell proliferation and migration were analyzed using MTT and transwell assays, respectively. Epithelial-mesenchymal transition markers were examined via Western blotting assay. RNA pull-down was used to examine the interaction between linc00261 and the NME1 mRNA transcript. Results: linc00261 is expressed in lower levels on breast cancer tissues than in paracarcinoma tissues. Reintroduction of linc00261 can inhibit the migration of breast cancer cells and arrest their proliferation. Additionally, linc00261 knockdown is sufficient to cause breast carcinoma tumorigenesis. We also found that linc00261 interacts with NME1 mRNA, protecting it from degradation. This protection leads to increased cellular levels of NME1, which functions as suppressor of tumor metastasis. Conclusion: Taken together, these data demonstrate detailed mechanistic links between the linc00261/NME1 axis and tumorigenesis and show that linc00261 might serve as a novel therapeutic target.