Taken together, the findings of our study demonstrate that miR-506 overexpression in HCT116-OxR cells enhances oxaliplatin sensitivity by inhibiting MDR1/P-gp expression via down-regulation of the Wnt/β-catenin pathway and thus provide a rationale for the development of miRNA-based strategies to reverse oxaliplatin resistance in CRC cells.

We report Shanghai Tian Ma Radio Telescope detections of several long carbonchain molecules at C and Ku band, including HC 3 N, HC 5 N, HC 7 N, HC 9 N, C 3 S, C 6 H and C 8 H toward the starless cloud Serpens South 1a. We detected some transitions (HC 9 N J=13-12 F=12-11 and F=14-13, H 13 CCCN J=2-1 F=1-0 and F=1-1, HC 13 CCN J=2-1 F=2-2, F=1-0 and F=1-1, HCC 13 CN J=2-1 F=1-0 and F=1-1) and resolved some hyperfine components (HC 5 N J=6-5 F=5-4, H 13 CCCN J=2-1 F=2-1) for the first time in the interstellar medium. The column densities of these carbon-chain molecules in a range of 10 12 -10 13 cm −2 are comparable to two carbon-chain molecule rich sources, TMC-1 and Lupus-1A. The abundance ratios are 1.00:(1.11±0.15):(1.47±0.18) for [H 13 CCCN]:[HC 13 CCN]:[HCC 13 CN]. This result implies that the 13 C isotope is also concentrated in the carbon atom adjacent to the nitrogen atom in HC 3 N in Serpens south 1a, which is similar to TMC-1. The [HC 3 N]/[H 13 CCCN] ratio of 78±9, the [HC 3 N]/[HC 13 CCN] ratio of 70±8, and the [HC 3 N]/[HCC 13 CN] ratio of 53±4 are also comparable to those in TMC-1. In any case, Serpens South 1a proves a testing ground for understanding carbon-chain chemistry.

The δ opioid receptor (DOR) is involved in the regulation of malignant transformation and tumor progression of hepatocellular carcinoma (HCC). However, regulation of the DOR in HCC remains poorly defined. We found that miR-874 was identified as a negative regulator of the DOR, which is a direct and functional target of miR-874 via its 3′ untranslated region (UTR). Moreover, miR-874 was downregulated in HCC and its expression was inversely correlated with DOR expression. Downregulation of miR-874 was also associated with larger tumor size, more vascular invasion, a poor TNM stage, poor tumor differentiation, and inferior patient outcomes. Functionally, overexpression of miR-874 in the HCC cell line SK-hep-1 inhibited cell growth, migration, in vitro invasion, and in vivo tumorigenicity. Furthermore, miR-874 overexpression suppressed the DOR, resulting in a downregulated epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK) phosphorylation. The EGFR activator—epidermal growth factor (EGF)—can rescue the proliferation and migration suppression induced by miR-874 overexpression, and the rescue effects of the EGF were blocked by an ERK inhibitor. Our study results suggest that miRNA-874 is a negative regulator of the DOR that can suppress tumor proliferation and metastasis in HCC by targeting the DOR/EGFR/ERK pathway, which may be a potential target for HCC treatment.

Background Circular RNAs (circRNAs) play important roles in cancer progression and metabolism regulation. Serine/glycine metabolism supports the growth of cancer cells by contributing to their anabolic demands and epigenome as well as by regulating their redox state. However, the role of circRNA in the regulation of serine/glycine metabolism has not been well elucidated. Methods Microarray analysis was used to screen differentially expressed novel circRNAs. qRT-PCR and FISH were utilized to analyzed the expression of circMYH9. CCK8, colony formation and FACS were used to analyze proliferation of colorectal cancer (CRC) cells. Xenograft experiments were used to analyze tumor growth in vivo. RNA-sequencing, immunoblot and LC–MS were used to identify the downstream metabolic pathway of circMYH9. ChIRP, Mass Spectrometry, RIP and RNA pulldown were utilized to test the interaction between circMYH9, hnRNPA2B1 and p53 pre-mRNA. ChIP-qPCR was used to analyze the binding sites of HIF-1α. Chemically-induced CRC mice were generated to evaluate the role of circMYH9 in tumorigenesis. Results We identified an intron-derived circRNA, circMYH9, which was significantly upregulated in CRC tissues. A higher circMYH9 level correlated with shorter relapse-free survival and overall survival of CRC patients. CircMYH9 promoted serine/glycine metabolism, the NAD + /NADH ratio, and glutathione recycling and inhibited reactive oxygen species (ROS) in a p53-dependent manner, impacting tumour growth. Mechanistically, circMYH9 destabilized the pre-mRNA of p53 by recruiting hnRNPA2B1 in the nucleus. hnRNPA2B1 bound to N6-methyladenosine sites on the 3' untranslated region of p53 pre-mRNA and maintained its stability. Moreover, a lack of amino acids led to an elevated level of ROS, resulting in increased HIF1α, which promoted circMYH9 expression by binding to the promoter region. Furthermore, in vivo AAV9-mediated transfection of circMYH9 could drive chemically-induced carcinogenesis by suppressing p53 in mice. Conclusions The overexpression of circMYH9 promotes CRC proliferation though modulating serine/glycine metabolism and redox homeostasis in a p53-dependent manner, and targeting circMYH9 and its pathway may be an effective strategy for the treatment of CRC.