Evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in the regulation of tumor cellular processes, such as proliferation, apoptosis, and metastasis. LncRNA CRNDE (Colorectal Neoplasia Differentially Expressed) is located at human chromosome 16 and has been found overexpressed in a variety of cancers including colorectal cancer (CRC). In this paper, we report that lncRNA CRNDE expression was remarkably upregulated in CRC tissues and that lncRNA CRNDE overexpression was positively correlated with advanced pathological stages and larger tumor sizes. In addition, the knockdown of CRNDE significantly suppressed proliferation and caused apoptosis of CRC cells both in vitro and in vivo. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA CRNDE could epigenetically suppress the expressions of dual-specificity phosphatase 5 (DUSP5) and CDKN1A by binding to EZH2 (the key components of Polycomb repressive complex 2 (PRC2)), thus promoting CRC development. In conclusion, our data suggest that the lncRNA CRNDE promotes the progression of CRC and is a potential therapeutic target for CRC intervention.

The strategy of using fecal microbiota transplantation (FMT) for refractory ulcerative colitis (UC) remains unclear if single FMT failed to induce remission. This study aimed to evaluate the efficacy and safety of a designed step-up FMT strategy for the steroid-dependent UC. Fifteen patients with steroid-dependent UC were enrolled, and treated with step-up FMT strategy. Follow-up clinical data was collected for a minimum of 3 months. Fecal microbiota composition before and post FMT of patients and related donors were analyzed by 16S rRNA sequencing. Eight of fourteen (57.1 %) patients achieved clinical improvement and were able to discontinue steroids following step-up FMT. One patient was lost to follow-up. Among the 8 patients who responded, five (35.7 %) received one FMT therapy, one (7.1 %) received two FMTs, and two (14.2 %) received two FMTs plus a scheduled course of steroids. Four (28.6 %) of the 8 patients who responded maintained long-term remission during follow-up (3–18 months). Six patients (42.9 %) failed to meet the criteria of clinical improvement and maintained steroid dependence, though three experienced transient or partial improvement. Microbiota analysis showed that FMT altered the composition greatly, and a microbiota composition highly similar to that of the donor emerged in the patients with successful treatment. No severe adverse events occurred during treatment and follow-up. Step-up FMT strategy shows promise as a therapeutic strategy for patients with steroid-dependent UC, likely due to the successful restructuring of gut microbial composition. Trial registration: ClinicalTrials.gov, Number NCT01790061

Fecal microbiota transplantation (FMT) has been used as a potential treatment option for Crohn’s disease (CD). However, there is still lack of safety and efficacy evidence based on large samples of CD undergoing FMT. This study aimed to evaluate the risk factors of adverse event (AE) in the long term and the efficacy of FMT in the short term for patients with CD.

T cells expressing chimeric antigen receptors, especially CD19 CAR-T cells have exhibited effective antitumor activities in B cell malignancies, but due to several factors such as antigen escape effects and tumor microenvironment, their curative potential in hepatocellular carcinoma has not been encouraging. To reduce the antigen escape risk of hepatocellular carcinoma, this study was to design and construct a bispecific CAR targeting c-Met and PD-L1. c-Met/PD-L1 CAR-T cells were obtained by lentiviral transfection, and the transfection efficiency was monitored by flow cytometry analysis. LDH release assays were used to elucidate the efficacy of c-Met/PD-L1 CAR-T cells on hepatocellular carcinoma cells. In addition, xenograft models bearing human hepatocellular carcinoma were constructed to detect the antitumor effect of c-Met/PD-L1 CAR-T cells in vivo. The results shown that this bispecific CAR was manufactured successfully, T cells modified with this bispecific CAR demonstrated improved antitumor activities against c-Met and PD-L1 positive hepatocellular carcinoma cells when compared with those of monovalent c-Met CAR-T cells or PD-L1 CAR-T cells but shown no distinct cytotoxicity on hepatocytes in vitro. In vivo experiments shown that c-Met/PD-L1 CAR-T cells significantly inhibited tumor growth and improve survival persistence compared with other groups. These results suggested that the design of single-chain, bi-specific c-Met/PD-L1 CAR-T is more effective than that of monovalent c-Met CAR-T for the treatment of hepatocellular carcinoma., and this bi-specific c-Met/PD-L1 CAR is rational and implementable with current T-cell engineering technology.

Background: A variety of miRNAs have been recently reported to be abnormally expressed in colorectal cancer (CRC). A growing number of studies have demonstrated that aberrantly expressed miRNAs are closely related to the development and progression of CRC. It has been found that miR-140-3p plays a vital role in several cancers. However, its expression, roles and mechanisms in CRC are remain unknown. Materials and methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine miR-140-3p expression in CRC tissues and cell lines. CCK8, migration, invasion and flow cytometric assays were used to determine the influence of miR-140-3p upregulation on cell proliferation, migration, invasion and apoptosis of CRC cells. Luciferase reporter assays and Western blots were utilized to identify the target genes of miR-140-3p. In addition, the potential mechanism of miR-140-3p action in CRC cells was elucidated. Results: In our study, miR-140-3p expression was significantly decreased in CRC tissues and cell lines. Overexpression of miR-140-3p attenuated proliferation, migration, and invasion and induced the apoptosis of CRC cells. Bioinformatics analyse and luciferase reporter analysis identified PD-L1 as a putative target gene of miR-140-3p. PD-L1 was overexpressed in CRC tissues and inversely correlated with miR-140-3p expression. Suppression of PD-L1 expression in CRC cells generated biological behaviours in CRC cells that were similar to those observed after treated with miR-140-3p mimics. Restoration of PD-L1 expression partially attenuated the inhibitory effect of miR-140-3p on CRC cells. Western blot were used to verify the effect of PD-L1 expression on PI3K/AKT pathway. In addition, overexpression of miR-140-3p could inhibit CRC tumor growth in vivo. Conclusion: In general, these data demonstrate that miR-140-3p acts as a tumour suppressor in CRC by directly targeting PD-L1 and inactivating PI3K/AKT pathway, suggesting that miR-140-3p might be a novel target for CRC diagnosis and treatment.