The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be overexpressed in colorectal cancer (CRC). However, its underlying mechanisms in the progression of CRC have not been well studied. To investigate the clinical significance of NEAT1, we analyzed its expression levels in a publicly available dataset and in 71 CRC samples from Fudan University Shanghai Cancer Center. Functional assays, including the CCK8, EdU, colony formation, wound healing, and Transwell assays, were used to determine the oncogenic role of NEAT1 in human CRC progression. Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and Dual-Luciferase Reporter Assays were used to determine the mechanism of NEAT1 in CRC progression. Animal experiments were used to determine the role of NEAT1 in CRC tumorigenicity and metastasis in vivo. NEAT1 expression was significantly upregulated in CRC tissues compared with its expression in normal tissues. Altered NEAT1 expression led to marked changes in proliferation, migration, and invasion of CRC cells both in vitro and in vivo. Mechanistically, we found that NEAT1 directly bound to the DDX5 protein, regulated its stability, and sequentially activated Wnt signaling. Our study showed that NEAT1 indirectly activated the Wnt/β-catenin signaling pathway via DDX5 and fulfilled its oncogenic functions in a DDX5-mediated manner. Clinically, concomitant NEAT1 and DDX5 protein levels negatively correlated with the overall survival and disease-free survival of CRC patients. Our findings indicated that NEAT1 activated Wnt signaling to promote colorectal cancer progression and metastasis. The NEAT1/DDX5/Wnt/β-catenin axis could be a potential therapeutic target of pharmacological strategies.

Background: The long non-coding RNAs (lncRNAs) study has gradually become one of the hot topics in the field of RNA biology. One lncRNA which has attracted attention is LOC285194, a lncRNA demonstrated the potential tumor-suppressor role in osteosarcoma. The aim of this study was to examine the expression of LOC285194 in colorectal cancer (CRC) patients and to investigate the relationship between this lncRNA levels and existing clinicopathologic parameters and patient survival. Methods: The expression of LOC285194 was detected by quantitative real-time polymerase chain reaction in pairs of tumorous and adjacent normal tissues of 81 colorectal cancer patients with a follow-up of 5 years, as well as in three colorectal cancer cell lines and normal intestinal mucous cell line. Then, we analyzed the potential relationship between this lncRNA levels in tumor tissues and existing clinicopathological features of CRC, and clinical outcome. Results: The relative expression levels of LOC285194 was significantly lower in tumor tissues (p < 0.001) and colorectal cancer cell lines compared with adjacent normal tissues and normal intestinal mucous cell line. In addition, low expression of LOC285194 was correlated with larger tumor size (p = 0.015), higher tumor stage (p = 0.034), and more distant metastasis (p = 0.046). Kaplan-Meier analysis indicated that patients with low LOC285194 expression had a poor disease free survival (p = 0.010). Moreover, multivariate analysis showed that decreased expression of LOC285194 was an independent predictor of disease-specific survival. Conclusion: Our data indicate that LOC285194 might be a novel prognostic indicator in colorectal cancer and may be a potential target for diagnosis and gene therapy.

Despite advances in anticancer therapy, the prognosis of gastric cancer (GC) remains unsatisfactory. Research in recent years has shown that the malignant behavior of cancer is not only attributable to tumor cells but is partly mediated by the activity of the cancer stroma and controlled by various molecular networks in the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are one of the most abundant mesenchymal cell components of the stroma and extensively participate in the malignant development of GC malignancy. CAFs modulate the biological properties of tumor cells in multiple ways, including the secretion of various bioactive molecules that have effects through paracrine and autocrine signaling, the release of exosomes, and direct interactions, thereby affecting GC initiation and development. However, there is marked heterogeneity in the cellular origins, phenotypes, and functions of CAFs in the TME of GC. Furthermore, variations in factors, such as proteins, microRNAs, and lncRNAs, affect interactions between CAFs and GC cells, although, the potential molecular mechanisms are still poorly understood. In this review, we aim to describe the current knowledge of the cellular features and heterogeneity of CAFs and discuss how these factors are regulated in CAFs, with a focus on how they affect GC biology. This review provides mechanistic insight that could inform therapeutic strategies and improve the prognosis of GC patients.

Increased expression of branched-chain amino acid transaminase 1 or 2 (BCAT1 and BCAT2) has been associated with aggressive phenotypes of different cancers. Here we identify a gain of function of BCAT1 glutamic acid to alanine mutation at codon 61 (BCAT1^E61A) enriched around 2.8% in clinical gastric cancer samples. We found that BCAT1^E61A confers higher enzymatic activity to boost branched-chain amino acid (BCAA) catabolism, accelerate cell growth and motility and contribute to tumor development. BCAT1 directly interacts with RhoC, leading to elevation of RhoC activity. Notably, the BCAA-derived metabolite, branched-chain α-keto acid directly binds to the small GTPase protein RhoC and promotes its activity. BCAT1 knockout-suppressed cell motility could be rescued by expressing BCAT1^E61A or adding branched-chain α-keto acid. We also identified that candesartan acts as an inhibitor of BCAT1^E61A, thus repressing RhoC activity and cancer cell motility in vitro and preventing peritoneal metastasis in vivo. Our study reveals a link between BCAA metabolism and cell motility and proliferation through regulating RhoC activation, with potential therapeutic implications for cancers.

Fructose-1,6-bisphosphatase (FBP1) is a rate-limiting enzyme in gluconeogenesis and an important tumor suppressor in human malignancies. Here, we aimed to investigate the expression profile of FBP1 in ovarian cancer, the molecular mechanisms that regulate FBP1 expression and to examine how the FBP1 regulatory axis contributes to tumorigenesis and progression in ovarian cancer. We showed that FBP1 expression was significantly decreased in ovarian cancer tissues compared with normal ovarian tissues, and low-FBP1 expression predicted poor prognosis in patients with ovarian cancer. The enhanced expression of FBP1 in ovarian cancer cell lines suppressed proliferation and 2-D/3-D invasion, reduced aerobic glycolysis, and sensitized cancer cells to cisplatin-induced apoptosis. Moreover, DNA methylation and C-MYC binding at the promoter inhibited FBP1 expression. Furthermore, through physical interactions with signal transducer and activator of transcription 3 (STAT3), FBP1 suppressed nuclear translocation of STAT3 and exerted its non-metabolic enzymatic activity to induce the dysfunction of STAT3. Thus, our study suggests that FBP1 may be a valuable prognostic predictor for ovarian cancer. C-MYC-dependent downregulation of FBP1 acted as a tumor suppressor via modulating STAT3, and the C-MYC/FBP1/STAT3 axis could be a therapeutic target.

Background: The long non-coding RNA Linc00152 stimulates tumor progression in cancer. However, its clinical significance and biological functions in lung adenocarcinoma remains unknown. We evaluate the expression of Linc00152 in lung adenocarcinoma and its possible correlation with clinicopathologic features and patient survival to reveal its biological effects in cancer progression and prognosis.