Background/Aims: Next-generation sequencing (NGS) has revealed abundant long noncoding RNAs (lncRNAs) that have been characterized as critical components of cancer biology in humans. The present study aims to investigate the role of the lncRNA KCNQ1OT1 in breast cancer (BRCA) as well as the underlying molecular mechanisms and functions of KCNQ1OT1 involved in the progression of BRCA. Methods: The Cancer Genome Atlas (TCGA) and StarBase v2.0 were used to obtain the required gene data. Dual luciferase reporter gene assays were conducted to verify the relevant intermolecular target relationships. QRT-PCR and Western blot were performed to measure the expression levels of different molecules. Cell proliferation was detected by using the MTT and colony formation assays, while cell migration and invasion were examined by transwell assay. Variations in cell apoptosis and cell cycle were determined through flow cytometry. A tumor xenograft model was applied to assess tumor growth in vivo. Results: KCNQ1OT1 was found to be remarkably highly expressed in BRCA tissues and cells. KCNQ1OT1 modulated CCNE2 through sponging miR-145 in BRCA. KCNQ1OT1 promoted tumor growth in vivo by regulating miR-145/CCNE2. Conclusion: The KCNQ1OT1/miR-145/CCNE2 axis plays a critical regulatory role in BRCA, potentially giving rise to BRCA tumorigenesis and progression. These findings provide valuable evidence for improving the diagnosis and treatment of BRCA in the future.

The protein encoded by immature colon carcinoma transcript 1 (ICT1) is a component of the human mitochondrial ribosome, and is reported to be implicated in cell proliferation, viability and apoptosis of HeLa cells. This study was conducted to investigate the role of ICT1 in human breast cancer. Oncomine database was used to investigate ICT1 expression in human breast cancer tissues compared to normal tissues. The results showed that ICT1 was highly overexpressed in various human breast cancer subtypes. Then short hairpin RNA (shRNA)-mediated knockdown of ICT1 was performed in human breast cancer ZR-75-30 and T-47D cells. A series of functional analysis, including MTT, colony formation and flow cytometry assays were conducted after ICT1 knockdown. Our results demonstrated that knockdown of ICT1 significantly suppressed cell viability and proliferation through cell cycle arrest at the G2/M phase and induced apoptosis in breast cancer cells. Furthermore, knockdown of ICT1 altered signaling pathways associated with cell growth and apoptosis, including phospho‑BAD (Ser112), phospho-PRAS40 (Thr246) and induction of phospho‑AMPKα (Thr172). Additionally, it was further confirmed by western blot analysis that ICT1 knockdown altered the expression of apoptosis- or cell cycle‑related proteins such as Bcl-2, caspase-3, CDK1, CDK2 and cyclin B. In conclusion, targeting ICT1 in breast cancer cells may provide a new strategy for breast cancer gene therapy.

BackgroundMale breast cancer (BC) is a kind of rare tumour. There were few researches concerning the effect of chemotherapy for it. The purpose of this study is to estimate the value of chemotherapy on prognosis in male BC.Patients and methodsComplete clinical and pathological information of male BC were collected from January 1990 to January 2008 in Zhejiang Cancer Hospital in China. 134 cases of male BC were included for analysis and separated into two groups based on receiving chemotherapy or not receiving chemotherapy. The disease-free survival (DFS) and overall survival (OS) between chemotherapy group and non-chemotherapy group were compared with Kaplan-Meier survival curve. Stratified analysis was used to evaluate the strength of the association between chemotherapy and each risk factor. Multivariate analysis was conducted by using COX proportional hazard regression model.ResultsThere were 58.21% (78/134) cases who underwent chemotherapy and 41.79% (56/134) cases without chemotherapy. There were 20 cases (25.64%) with recurrence/metastasis in patients with chemotherapy and six cases (10.71%) in patients without chemotherapy. The mean DFS time of male BC with chemotherapy and non-chemotherapy is 150.87 and 154.13 months, respectively (χ2=3.825, p=0.050). The mean OS time of male BC with chemotherapy and non-chemotherapy is 155.33 and 154.26 months, respectively (χ2=2.542, p=0.111). COX proportional hazard regression model showed that the two groups had similar DFS (HR=0.386, p=0.165), while chemotherapy might be a protective fact on OS (HR=0.140, p=0.026).ConclusionThe utility of chemotherapy should be considered in the high risk level of recurrence/metastasis in male BC.

Abstract. The present study aimed to detect the differences between breast cancer cells and normal breast cells, and investigate the potential pathogenetic mechanisms of breast cancer. The sample GSE9574 series was downloaded, and the microarray data was analyzed to identify differentially expressed genes (DEGs). Gene Ontology (GO) cluster analysis using the GO Enrichment Analysis Software Toolkit platform and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for DEGs was conducted using the Gene Set Analysis Toolkit V2. In addition, a protein-protein interaction (PPI) network was constructed, and target sites of potential transcription factors and potential microRNA (miRNA) molecules were screened. A total of 106 DEGs were identified in the current study. Based on these DEGs, a number of bio-pathways appear to be altered in breast cancer, including a number of signaling pathways and other disease-associated pathways, as indicated by KEGG pathway clustering analysis. ATF3, JUND, FOSB and JUNB were detected in the PPI network. Finally, the most significant potential target sites of transcription factors and miRNAs in breast cancer, which are important in the regulation of gene expression, were identified. The results indicated that miR-93, miR-302A, miR-302B, miR-302C, miR-302D, miR-372, miR-373, miR-520E and miR-520A were closely associated with the occurrence and development of breast cancer. Therefore, changes in the expression of these miRNAs may alter cell metabolism and trigger the development of breast cancer and its complications.

We aimed to investigate the potential role and regulatory mechanism of long noncoding RNA tumor‐associated lncRNA expressed in chromosome 2 (TALNEC2) in breast cancer. The expression of TALNEC2 in breast cancer tissues and cells were investigated. MCF‐7 and MDA‐MB‐231 cells were transfected with small interfering RNA (siRNA) duplexes for targeting TALNEC2 (si‐TALNEC2), enhancer of zeste homolog 2 (EZH2; si‐EZH2) and p57KIP2 (si‐p57 KIP2), and their corresponding controls (si‐NC). The viability, colony forming ability, cell cycle, apoptosis, and autophagy of transfected cells were assessed. The expressions of p‐p38 mitogen‐activated protein kinase (MAPK) and nuclear factor κB (NF‐κB) pathway‐related proteins were investigated. The results showed that TALNEC2 was highly expressed in breast cancer tissues and cells. Knockdown of TALNEC2 significantly inhibited the malignant behaviors of MCF‐7 and MDA‐MB‐231 cells, including inhibiting cell viability and colony forming, arresting cell cycle at G0/G1 phase, inducing cell apoptosis, and promoting cell autophagy. EZH2 was a TALNEC2 binding protein, which was upregulated in breast cancer tissues and cells and could negatively regulate p57 KIP2. Effects of TALNEC2 knockdown on malignant behaviors of MCF‐7 cells were reversed by p57 KIP2 knockdown. The expressions of p‐p38, RelA, and RelB in MCF‐7 cells were decreased after knockdown of TALNEC2 or EZH2, which were reversed by knockdown of p57 KIP2 concurrently. In conclusion, TALNEC2 may play an oncogenic role in breast cancer by binding to EZH2 to target p57 KIP2. Activation of p‐p38 MAPK and NF‐κB pathways may be key mechanisms mediating the oncogenic role of TALNEC2 in breast cancer. TALNEC2 may serve as a promising target in the therapy of breast cancer.