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Recent researches have reported that long noncoding RNA (lncRNA) five prime to Xist (FTX) plays a crucial role in the initiation and progression of cancers. In the current study, the clinical significance and functional roles of lncRNA FTX in colorectal cancer (CRC) progression were investigated. A significant increase of lncRNA FTX expression in CRC tissue and cell lines was observed. Overexpression of lncRNA FTX was significantly associated with the bigger tumor diameter, the advanced TNM stage, the lymph node, and distant metastasis, and also predicted poor prognosis of patients with CRC. Functional analyses demonstrated that knockdown of lncRNA FTX markedly inhibited CRC cell proliferation, migration, and invasion in vitro. Mechanistically, FTX directly interacted with miR-215 and suppressed miR-215 expression. FTX also bind to vimentin and reduced its phosphorylation level on Ser83 in CRC cells. Finally, using siRNAs against lncRNA FTX could dramatically inhibit CRC growth and distant metastasis in vivo. Taken together, our data demonstrated an oncogenic role of lncRNA FTX in CRC tumorigenesis and progression via interaction with miR-215 and vimentin. Then, a promising therapeutic target for CRC was provided.

Tumor cells switch from an epithelial to a mesenchymal-like phenotype, which represents a key hallmark of human cancer metastasis, including gallbladder cancer (GBC). A large set of microRNAs (miRNAs/miRs) have been studied to elucidate their functions in initiating or inhibiting this phenotypic switching in GBC cells. In this paper, we attempted to identify the expression pattern of the miR-214/-3120 cluster and its mode of action in the context of GBC, with a specific focus being placed on their effects on EMT and autophagy in GBC cells. Human GBC cells GBC-SD were assayed for their migration, invasion, and autophagy using the Transwell chamber system, MDC staining, and transmission electron microscopy. The tumorigenicity and metastatic behavior of GBC-SD cells were tested in nude mice. The expression of EMT- and autophagy-specific markers (E-cadherin, N-cadherin, vimentin, ATG5, LC3II/LC3I, and Beclin1) was analyzed in cultured GBC-SD cells and in human GBC-SD xenografts. The E2F3 luciferase reporter activity in the presence of miR-214/-3120 was evaluated by a dual luciferase assay. The miR-214/-3120 was downregulated in GBC. Exogenous miR-214/-3120 inhibited the phenotypic switching of GBC cells from epithelial to mesenchymal, prevented autophagy, and suppressed the tumorigenicity and metastatic behavior of GBC-SD cells in vitro and in vivo. E2F3 was demonstrated to be the target gene of miR-214/-3120, and its knockdown in part mimicked the effect of miR-214/-3120 on the EMT, autophagy, tumorigenicity, and metastatic behavior of GBC-SD cells. These results demonstrated that the miR-214/-3120 cluster blocks the process of EMT and autophagy to limit GBC metastasis by repressing E2F3 expression.

The present study was conducted to investigate the molecular mechanism of urotensin II (UII) and its receptor, G protein‑coupled receptor 14 (GPR14), in colonic inflammation. Urantide, a special antagonist of GPR14, and GPR14-siRNA were used to inhibit GPR14 signaling in dextran sulfate sodium (DSS)‑induced inflammation in mice and Caco-2 cells. The results showed that urantide alleviated rectal bleeding, histological injury and production of interleukin (IL)-17 and tumor necrosis factor‑α (TNF‑α) caused by DSS in mice. GPR14-siRNA transfection subsequent with GPR14 inhibition reduced DSS-induced interferon-γ (IFN)-γ production in Caco-2 cells. Meanwhile, both in vivo and in vitro data demonstrated that inhibition of UII/GPR14 alleviated nuclear factor-κB (NF-κB) activation caused by DSS. In conclusion, UII/GPR14 signaling was involved in the DSS-induced colonic inflammation and its inhibition may serve as a potential therapeutic target, which may be associated with the NF-κB signaling pathway.

Histone deacetylases (HDACs) can regulate cell-cycle, differentiation, and apoptosis of hepatocarcinoma (HCC) cells, while their roles in drug sensitivity remain unclear. Our results showed that the expression of HDAC2 was significantly increased in HCC doxorubicin (Dox) resistant cells as compared with their corresponding control cells. Over expression of HDAC2 can increase the cell viability and decrease the Dox sensitivity. Kaplan-Meier Plotter assay revealed that HCC patients with higher levels of HDAC2 had significantly poor prognosis than that of the lower expression patients. Mechanistically studies revealed that HDAC2 can regulate the transcription of ABCB1 via directly binding with its promoter and increasing its expression in Dox resistant HCC cells. Knockdown of HDAC2 significantly inhibited the expression of ABCB1. Co-immunoprecipitation revealed that HDAC2 can bind with c-fos, an important transcription factor of ABCB1, in HCC/Dox cells. Knockdown of c-Fos decreased the binding between HDAC2 and promoter of ABCB1 in HCC/Dox cells. Collectively, our data revealed that HDAC2 can regulate Dox sensitivity of HCC cells and the transcription of ABCB1.

Background The 3D structure and functions of ENPP4, a protein expressed on the surface of Bacillus Calmette–Guerin (BCG)-activated macrophages, are unknown. In this study, we analyzed the 3D structure of ENPP4 and determined its tumoricidal effects on MCA207 cells. Results Homology modeling showed that Arg305, Tyr341, Asn291, and Asn295 are important residues in substrate, adenosine triphosphate (ATP), binding. A molecular dynamics study was also carried out to study the stability of ENPP4 (including zinc atoms) as well as its ligand–enzyme complex. BCG increased ENPP4 expression in macrophages, and specific blocking of ENPP4 in BCG-activated macrophages (BAMs) significantly reduced their cytotoxicity against MCA207 cells. Conclusions These results indicate that zinc remains inside the ENPP4 protein, a BCG activated tumoricidal macrophage protein, throughout the simulation. Important information for the design of new inhibitors was obtained. Electronic supplementary material The online version of this article (doi:10.1186/s12944-016-0189-4) contains supplementary material, which is available to authorized users.