Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts shown to play important roles in tumourigenesis and tumour progression. Our study aimed to examine expression of the lncRNA MAGI2-AS3 in breast cancer and to explore its function in cancer cell growth. First, MAGI2-AS3 expression levels in clinical samples and cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The functional significance of MAGI2-AS3 in cancer cell proliferation and apoptosis was then examined in vitro. Our results showed MAGI2-AS3 to be down-regulated in breast cancer tissues compared to normal adjacent tissues. Moreover, MAGI2-AS3 markedly inhibited breast cancer cell growth and increased expression of Fas and Fas ligand (FasL). In conclusion, our data suggest that MAGI2-AS3 expression is decreased in breast cancer and that MAGI2-AS3 plays an important role as a tumour suppressor by targeting Fas and FasL signalling. These results provide new insight into novel clinical treatments for breast cancer.

No abstract

Breast cancer is characterized by an elevated capacity for tumor invasion and lymph node metastasis, but the cause remains to be determined. Recent studies suggest that microRNAs (miRNAs) can regulate the evolution of malignant behavior by regulating multiple target genes. A key oncomir in carcinogenesis is miR-21, which is consistently upregulated in a wide range of cancers. However, few functional studies are available for miR-21, and few targets have been identified. In this study, we explored the role of miR-21 in human breast cancer cells and searched for miR-21 targets.Total RNA from breast cancer tissue and corresponding adjacent normal tissue was extracted and used to detect miR-21 expression by quantificational real-time polymerase chain reaction (qRT-PCR), followed by analysis of the correlation between gonad hormone indices in peripheral blood and miR-21 expression in cancerous tissues from the same patients. Cell proliferation, colony formation, migration and invasion were then examined to determine the role of miR-21 in regulating breast cancer cells. Finally, western blotting was performed to determine if miR-21 regulated expression of signal transducers and activators of transcription 3 (STAT3), and assays of cell proliferation, colony formation, migration and invasion were performed to examine the role of STAT3 in regulation of breast cancer cells. We found that expression of miR-21 increased from normal through benign to cancerous breast tissues. Enhanced miR-21 expression was associated with serum levels of follicle-stimulating hormone, estradiol, β-human chorionic gonadotropin, testosterone and prolactin in patients with breast cancer. Furthermore, cell proliferation, colony formation, migration and invasion were increased after overexpression of miR-21 in breast cancer cells and reduced by miR-21 suppression. In addition, we identified a putative miR-21 binding site in the 3'-untranslated region of the STAT3 gene using an online bioinformatical tool. We found that protein expression of STAT3 was significantly downregulated when breast cancer cells were transfected with miR-21 mimics, and was significantly upregulated in breast cancer cells transfected with a miR-21 inhibitor. Finally, we found that cell proliferation, colony formation, migration and invasion were decreased by treatment with 2.5 nM of Stattic, an inhibitor of STAT3 activation. Our data suggest that miR-21 expression is increased in breast cancer and plays an important role as a tumor gene by targeting STAT3, which may act as a double-response controller in breast cancer.

Abstract. MicroRNA (miRNA) is a type of endogenous non-coding RNA implicated in various cellular processes. Studies have shown that miR-124 is involved in the malignant progression of cancer, but little is known concerning its potential role in breast cancer. Therefore, the purpose of this study was to conduct a functional analysis of miR-124 in breast cancer, and to identify its target genes in this disease. To this end, we used quantitative real-time PCR to examine the expression level of miR-124 in breast cancer tissue specimens and cell lines. To study the functional significance of miR-124, we overexpressed miR-124 with miR-124 mimics and observed breast cancer cell proliferation, colony formation, migration, and invasion abilities by in vitro cell culture experiments. Target prediction algorithms and luciferase reporter gene assays were used to identify the target genes of miR-124. We also knocked down miR-124 targets using short hairpin RNA (shRNA) constructs, and observed associated breast cancer cell characteristics by in vitro cell culture experiments. We found that miR-124 expression significantly decreased in breast cancer tissues and cells compared to normal tissues and cells. In addition, cell proliferation, colony formation, migration, and invasion were decreased after overexpression of miR-124 in breast cancer cells. Furthermore, we used several algorithms to identify the snail family zinc finger 2 (SNAI2) as a potential target gene of miR-124. The protein expression level and luciferase activity of the 3'-untranslated region of SNAI2 were significantly decreased in breast cancer cells transfected with miR-124 mimics. Cell proliferation, colony formation, migration, and invasion were also decreased after knockdown of SNAI2 by shRNA. In conclusion, our data suggest that miR-124 expression is decreased in breast cancer and plays an important role as a tumor suppressor gene by targeting SNAI2. These findings may reveal novel perspectives for clinical treatments against breast cancer.

Purpose: Yes-associated protein 1 (YAP1) is overexpressed in head and neck squamous cell carcinoma (HNSCC). However, it is unknown whether verteporfin, a YAP1 inhibitor, can inhibit HNSCC cells as well as the molecular mechanisms involved. Methods: YAP1 expression was investigated by immunohistochemistry in human head and neck carcinoma tissues (n=70). CCK-8 assay, colony formation assay, flow cytometric analysis, wound-healing assay and Transwell migration and invasion assays were used to evaluated the effects of verteporfin on the six HNSCC cell lines (three HPV-positive and three HPV-negative). The transcription and protein expression levels of YAP1 and its associated genes were investigated by real-time PCR and Western blotting, respectively. The effects of verteporfin on HNSCC cells in vivo were assessed by a xenograft model. Results: YAP1 expression was significantly higher in carcinoma tissues than in tumor-adjacent normal tissues (n=10). A CCK-8 assay showed that the inhibitory effects of verteporfin on HNSCC cells were markedly enhanced by light activation. Verteporfin significantly inhibited HNSCC cell proliferation, migration and invasion, induced apoptosis, and arrested the cell cycle at the S/G2 phase. Verteporfin significantly attenuated the expression of genes related to epithelial-mesenchymal transition (YAP1, Snail, CTNNB1 and EGFR) and stemness (Oct4 and YAP1) and increased E-cadherin expression in HNSCC cells. Furthermore, verteporfin significantly inhibited PD-L1 expression in HNSCC cells. However, the expression levels of HPV-16 E6 and E7 did not change with VP treatment. The anticancer effect of verteporfin on HNSCC was confirmed by the inhibition of xenograft growth in vivo. Conclusions: Our results indicate that YAP1 overexpression is involved in HNSCC tumorigenesis and verteporfin is a potential therapeutic drug for HNSCC.

Long noncoding RNAs (lncRNAs) have been suggested to play vital roles in tumor initiation and progression. Recent studies have reported that the lncRNA small nucleolar RNA host gene 16 (SNHG16) is highly expressed in breast cancer tissue. In the present study, we demonstrated that SNHG16 is an oncogene involved in cell proliferation and invasion in breast cancer. First, we examined the functional role of SNHG16 in breast cancer cells by knocking down SNHG16 expression via siRNA. We found that SNHG16 inhibition reduced the proliferation and invasion of breast cancer cells in vitro. Then, based on bioinformatic prediction and functional assay validation, we demonstrated SNHG16 interaction with miR-30a and its role in breast cancer cells. Finally, we examined the functional role of RRM2 in breast cancer cells by knocking down RRM2 expression via siRNA. Our results indicated that the SNHG16/miR-30a axis regulated the expression of ribonucleotide reductase M2 (RRM2) in breast cancer cells. These results provide novel insight into breast cancer tumorigenesis and suggest that SNHG16 could serve as a therapeutic target in breast cancer.

No abstract

Nowadays, primary liver cancer is still a major threat to human health. Anoikis is a particular form of programed cell death that has an inhibitory effect on neoplasm metastasis. Although several prognostic models based on anoikis‐related genes for Hepatocellular carcinoma (HCC) have been established, signatures associated with anoikis‐related lncRNAs have not been identified. To fill this blank space, the authors built up a prognostic signature and appraised its value in guiding immunotherapy. Eleven prognostic anoikis‐related lncRNAs were identified through Least Absolute Shrinkage and Selection Operator Cox analysis. The accuracy of the risk signature in predicting prognosis was verified by K–M survival analysis and Receiver operating characteristic analysis. We further discovered that the high‐risk group was often enriched in signal pathways related to cell growth and death and immune response; in addition, in the low‐risk group, cells often undergo metabolic changes through gene set enrichment analysis. Finally, we realised that HCC patients in the high‐risk group were upregulated in immune‐checkpoint molecules and tend to have a higher tumour mutation burden level which indicated a higher sensitivity to immunotherapy. All in all, the anoikis‐related lncRNAs risk signature showed excellent ability in predicting prognosis and may guide the application of immunotherapy in future clinical practice.