Although liver cancer is a malignant tumor with the highest mortality across the world, its pathogenesis and therapeutic targets remain unclear. Apoptosis, a natural cell death mechanism, is an important target of anticancer therapy. The discovery of effective apoptotic regulators can lead to the identification of novel therapeutic targets for treating cancer. Neurotrophin 3 (NTF3) is a member of the nerve growth factor (NGF) family that is involved in the progression of various cancers, including medulloblastoma, primitive neuroectodermal brain tumors, and breast cancer. NTF3 is under-expressed in human hepatocellular carcinoma (HCC), albeit its specific effects and the action mechanism have not been elucidated. Here, we confirmed that NTF3 expression was significantly low in HCC with reference to the GSEA database. By collecting patient data from our center and performing qRT-PCR analysis, we found that NTF3 expression was significantly downregulated in 74 patients with HCC. Low NTF3 expression was associated with a shorter overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). Both in vivo and in vitro experiments revealed that NTF3 considerably inhibited the progression of HCC cells. We found that the ligand NTF3 is regulated by c-Jun and binds to the p75 neurotrophin receptor (p75NTR) and then activates the JNK and P38 MAPK pathways to induce apoptosis. Entinostat (the target of HDAC1/HDAC3) can activate the NTF3/p75NTR pathway. These results indicate that NTF3 is a tumor suppressor, and that its low expression can help in predict poor clinical outcomes in HCC. Therefore, NTF3 can be used as a potential treatment molecule for HCC.

Long non-coding RNAs (LncRNAs) act as competing endogenous RNAs (ceRNAs) in colon cancer (CC) progression, via binding microRNAs (miRNAs) to regulate the expression of corresponding messenger RNAs (mRNAs). This article aims to explore the detailed molecular mechanism of ceRNA in CC. Top mad 5000 lncRNAs and top mad 5000 mRNAs were used to perform weighted gene co-expression network analysis (WGCNA), and key modules were selected. We used 405 lncRNAs in the red module and 145 mRNAs in the purple module to build the original ceRNA network by online databases. The original ceRNA network included 50 target lncRNAs, 41 target miRNAs, and 34 target mRNAs. Fifty target lncRNAs were used to establish a prognostic risk model by univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. LncRNAs in the risk model were used to build the secondary ceRNA network, which contained 9 lncRNAs in the risk model, 35 miRNAs, and 29 mRNAs. Survival analyses of 29 mRNAs in the secondary ceRNA network have shown HOXA10 and NHLRC3 were identified as crucial prognostic factors. Finally, we constructed the last ceRNA network including 5 lncRNAs in the risk model, 8 miRNAs, and 2 mRNAs related to prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR) results revealed that DNMBP-AS1 and FAM87A were down-regulated in CC cells and tissues. Function assays showed that over-expression of DNMBP-AS1 and FAM87A inhibited CC cells proliferation and migration. Mechanism study showed that DNMBP-AS1 served as miR-93-5p/17-5p sponges and relieved the suppression effect of miR-93-5p/17-5p on their target NHLRC3. Our study suggested that DNMBP-AS1 inhibited the progression of colon cancer through the miR-93-5p/17-5p/NHLRC3 axis, which could be potential therapeutic targets for CC.

Breast cancer is the most prevalent malignancy among females, but the molecular mechanisms involved in its pathogenesis and progression have remained to be fully elucidated. The aim of the present study was to identify novel potential therapeutic targets for breast cancer. The dataset GSE76275 was downloaded from the Gene Expression Omnibus database and weighted gene co‑expression network analysis (WGCNA) was performed to identify hub genes. Furthermore, the dataset GSE25055, containing gene expression data and clinical information, was downloaded to validate the expression and survival association of these hub genes. In addition, the datasets GSE25065 and GSE42568 were used to validate the association between hub gene expression levels and clinical features. Immunohistochemistry (IHC), reverse transcription‑quantitative PCR, as well as proliferation, migration, invasion and apoptosis assays, were used to verify gene expression and function. A total of 4,052 genes were selected for WGCNA and 18 modules were established; the red module was identified as the key module, as it had a strong positive correlation with the tumor grade. Survival analyses of hub genes [S‑adenosylmethionine decarboxylase proenzyme (AMD1), homeobox protein engrailed‑1 (EN1) and vestigial‑like protein (VGLL1)] indicated that higher levels of gene expression were associated with poor prognosis of patients with breast cancer. This association was based on survival analysis of GSE25055 using the Kaplan‑Meier plotter tool. Expression validation revealed that the upregulation of hub genes was associated with advanced tumor grade and malignant molecular subtype (basal‑like). IHC results from the Human Protein Atlas also demonstrated that protein expression levels of the hub genes were higher in tumor tissues compared with those in adjacent normal tissues. Furthermore, the expression levels of AMD1, EN1 and VGLL1 were strongly correlated with each other. These results demonstrated that AMD1 is highly expressed in breast cancer tissues and cells and AMD1 knockdown decreased the proliferation and metastatic potential, while increasing apoptosis of breast cancer cells. These results suggested that AMD1, EN1 and VGLL1 are likely to contribute to breast cancer progression and unfavorable prognosis.

Wiskott–Aldrich syndrome protein-interacting protein family member 1 (WIPF1) is associated with malignant tumor progression. However, molecular links between WIPF1 and gastric cancer (GC) remain elusive. The expression of WIPF1 was detected in GC tissues and cells. WIPF1 was overexpressed in GC tissues and cells and high expression of WIPF1 was an independent risk factor for a poor prognosis in patients with GC. Further experiments indicated that WIPF1 promoted the proliferation, invasion, and migration of GC cells in vivo and in vitro. WIPF1-regulated genes were closely related to cell proliferation and migration in GC, and silencing WIPF1 significantly repressed PI3K/AKT signaling pathway activation. WIPF1 was activated by myocardin (MYOCD) translation. Rescue experiments confirmed that MYOCD promotes the proliferation, invasion, and migration of GC cells in a WIPF1-dependent manner and activates the PI3K/AKT signaling pathway. MYOCD may transactivate WIPF1 and facilitate GC cell growth and metastasis by activating the PI3K/AKT signaling pathway.