PurposeThis study aimed to probe into the associations among circular RNA ZFR (circ-ZFR), miR-130a/miR-107, and PTEN, and to investigate the regulatory mechanism of circ-ZFR‒miR-130a/miR-107‒PTEN axis in gastric cancer (GC).Materials and MethodsGSE89143 microarray data used in the study were acquired from publicly available Gene Expression Omnibus database to identify differentially expressed circular RNAs inGC tissues. The expressions of circ-ZFR, miR-130a, miR-107, and PTEN were examined by real-time reverse transcription polymerase chain reaction, while PTEN protein expression was measured by western blot. The variation of GC cell proliferation and apoptosis was confirmed by cell counting kit-8 assay and flow cytometry analysis. The targeted relationships among circZFR, miR-130a/miR-107, and PTEN were predicted via bioinformatics analysis and demonstrated by dual-luciferase reporter assay and RNA immunoprecipitation assay. The impact of ZFR on gastric tumor was further verified in xenograft mice model experiment.ResultsCirc-ZFR and PTEN were low-expressed whereas miR-107 and miR-130a were highexpressed in GC tissues and cells. There existed targeted relationships and interactions between miR-130a/miR-107 and ZFR/PTEN. Circ-ZFR inhibited GC cell propagation, cell cycle and promoted apoptosis by sponging miR-107/miR-130a, while miR-107/miR-130a promoted GC cell propagation and impeded apoptosis through targeting PTEN. Circ-ZFR inhibited cell proliferation and facilitated apoptosis in GC by sponging miR-130a/miR-107 and modulating PTEN. Circ-ZFR curbed GC tumor growth and affected p53 protein expression in vivo.ConclusionCirc-ZFR restrained GC cell proliferation, induced cell cycle arrest and promoted apoptosis by sponging miR-130a/miR-107 and regulating PTEN.

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Intratumor heterogeneity (ITH) leads to an underestimation of the mutational landscape portrayed by a single needle biopsy and consequently affects treatment precision. The extent of colorectal cancer (CRC) genetic ITH is not well understood in Chinese patients. Thus, we conducted deep sequencing by using the OncoGxOne™ Plus panel, targeting 333 cancer-specific genes in multi-region biopsies of primary and liver metastatic tumors from three Chinese CRC patients. We determined that the extent of ITH varied among the three cases. On average, 65% of all the mutations detected were common within individual tumors. KMT2C aberrations and the NCOR1 mutation were the only ubiquitous events. Subsequent phylogenetic analysis showed that the tumors evolved in a branched manner. Comparison of the primary and metastatic tumors revealed that PPP2R1A (E370X), SETD2 (I1608V), SMAD4 (G382T), and AR splicing site mutations may be specific to liver metastatic cancer. These mutations might contribute to the initiation and progression of distant metastasis. Collectively, our analysis identified a substantial level of genetic ITH in CRC, which should be considered for personalized therapeutic strategies.

The lung is the most common extra-abdominal site of metastasis in colorectal cancer (CRC), in which circular RNA (circRNA) may have a crucial role. Therefore, the present study detected circRNA expression to identify novel targets to further study lung metastasis in CRC. In the present study, total RNA was extracted from CRC tissues of patients with and without lung metastasis to perform high-throughput microarray assay in order to detect differentially expressed circRNA. Following this, gene ontology (GO) and pathway analyses of the genes producing differentially expressed circRNA were performed to predict the function of circRNA using standard enrichment computational methods. Additionally, the circRNA/microRNA (miRNA) interactions were constructed with bioinformatics methods to predict the binding of miRNA with circRNA. In the CRC tissues from patients with lung metastasis, 431 circRNA were detected to be differentially expressed, including 192 upregulated and 239 downregulated over 2-fold compared with the CRC tissues without metastasis. Furthermore, GO analysis revealed that the genes producing upregulated circRNA were involved in DNA repair, while the genes producing downregulated circRNA were enriched in signal transduction. By pathway analysis, it was identified that the genes producing downregulated circRNA were involved in the nuclear factor-κB and Wnt signaling pathway in the CRC tissues from patients with lung metastasis compared with the CRC tissues without metastasis. In addition, it was demonstrated that hsa_circRNA_105055, hsa_circRNA_086376 and hsa_circRNA_102761 could commonly bind with miR-7 regulating target genes PRKCB, EPHA3, BRCA1 and ABCC1. The findings of the present study may provide a novel perspective on circRNA and lay a foundation for future research of potential roles of circRNA in CRC with lung metastasis.

Heroin addiction and withdrawal influence multiple physiological functions, including immune responses, but the mechanism remains largely elusive. The objective of this study was to investigate the molecular inflammatory interactome, particularly the cytokines and transcriptome regulatory network in heroin addicts undergoing withdrawal, compared to healthy controls (HCs). Twenty-seven cytokines were simultaneously assessed in 41 heroin addicts, including 20 at the acute withdrawal (AW) stage and 21 at the protracted withdrawal (PW) stage, and 38 age- and gender-matched HCs. Disturbed T-helper(Th)1/Th2, Th1/Th17, and Th2/Th17 balances, characterized by reduced interleukin (IL)-2, elevated IL-4, IL-10, and IL-17A, but normal TNF-α, were present in the AW subjects. These imbalances were mostly restored to the baseline at the PW stage. However, the cytokines TNF-α, IL-2, IL-7, IL-10, and IL-17A remained dysregulated. This study also profiled exosomal long non-coding RNA (lncRNA) and mRNA in the plasma of heroin addicts, constructed co-expression gene regulation networks, and identified lncRNA-mRNA-pathway pairs specifically associated with alterations in cytokine profiles and Th1/Th2/Th17 imbalances. Altogether, a large amount of cytokine and exosomal lncRNA/mRNA expression profiling data relating to heroin withdrawal was obtained, providing a useful experimental and theoretical basis for further understanding of the pathogenic mechanisms of withdrawal symptoms in heroin addicts.