Long non-coding RNAs (lncRNAs) are well known as crucial regulators to breast cancer development and are implicated in controlling autophagy. LncRNAs are also emerging as valuable prognostic factors for breast cancer patients. It is critical to identify autophagy-related lncRNAs with prognostic value in breast cancer. In this study, we identified autophagy-related lncRNAs in breast cancer by constructing a co-expression network of autophagy-related mRNAs-lncRNAs from The Cancer Genome Atlas (TCGA). We evaluated the prognostic value of these autophagy-related lncRNAs by univariate and multivariate Cox proportional hazards analyses and eventually obtained a prognostic risk model consisting of 11 autophagy-related lncRNAs (U62317.4, LINC01016, LINC02166, C6orf99, LINC00992, BAIAP2-DT, AC245297.3, AC090912.1, Z68871.1, LINC00578 and LINC01871). The risk model was further validated as a novel independent prognostic factor for breast cancer patients based on the calculated risk score by Kaplan-Meier analysis, univariate and multivariate Cox regression analyses and time-dependent receiver operating characteristic (ROC) curve analysis. Moreover, based on the risk model, the low-risk and high-risk groups displayed different autophagy and oncogenic statues by principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) functional annotation. Taken together, these findings suggested that the risk model of the 11 autophagy-related lncRNAs has significant prognostic value for breast cancer and might be autophagy-related therapeutic targets in clinical practice.

Pyruvate kinase M2 (PKM2), playing a central role in regulating aerobic glycolysis, was considered as a promising target for cancer therapy. However, its role in cancer metastasis is rarely known. Here, we found a tight relationship between PKM2 and breast cancer metastasis, demonstrated by the findings that beta-elemene (β-elemene), an approved drug for complementary cancer therapy, exerted distinct anti-metastatic activity dependent on PKM2. The results indicated that β-elemene inhibited breast cancer cell migration, invasion in vitro as well as metastases in vivo. β-Elemene further inhibited the process of aerobic glycolysis and decreased the utilization of glucose and the production of pyruvate and lactate through suppressing pyruvate kinase activity by modulating the transformation of dimeric and tetrameric forms of PKM2. Further analysis revealed that β-elemene suppressed aerobic glycolysis by blocking PKM2 nuclear translocation and the expression of EGFR, GLUT1 and LDHA by influencing the expression of importin α5. Furthermore, the effect of β-elemene on migration, invasion, PKM2 transformation, and nuclear translocation could be reversed in part by fructose-1,6-bisphosphate (FBP) and L-cysteine. Taken together, tetrameric transformation and nuclear translocation of PKM2 are essential for cancer metastasis, and β-elemene inhibited breast cancer metastasis via blocking aerobic glycolysis mediated by dimeric PKM2 transformation and nuclear translocation, being a promising anti-metastatic agent from natural compounds.

Non-small cell lung cancer (NSCLC) accounts for most lung cancer. To develop new therapy required the elucidation of NSCLC pathogenesis. The deubiquitinating enzymes USP 28 has been identified and studied in colon and breast carcinomas. However, the role of USP28 in NSCLC is unknown. The level mRNA or protein level of USP28 were measured by qRT-PCR or immunohistochemistry (IHC). The role of USP28 in patient survival was revealed by Kaplan-Meier plot of overall survival in NSCLC patients. USP28 was up or down regulated by overexpression plasmid or siRNA transfection. Cell proliferation and apoptosis was assayed by MTT and FACS separately. Potential microRNAs, which targeted USP28, were predicated by bioinformatic algorithm and confirmed by Dual Luciferase reporter assay system. High mRNA and protein level of USP28 in NSCLC were both correlated with low patient survival rate. Overexpression of USP28 promoted NSCLC cells growth and vice versa. Down-regulation of USP28 induced cell apoptosis. USP28 was targeted by miR-4295. Overexpression of USP28 promoted NSCLC cells proliferation, and was associated with poor prognosis in NSCLC patients. The expression of USP28 may be regulated by miR-4295. Our data suggested that USP28 was a tumour-promoting factor and a promising therapeutic target for NSCLC.