LncRNAs serve as novel biomarkers for diagnosis and prognosis of childhood ALL.

BACKGROUND: Although some studies have demonstrated that lncRNAs are dysregulated in hematopoietic malignancies and may regulate the progression of leukemia, the detailed mechanism underlying tumorigenesis is still unclear. This study aimed to investigate lncRNAs that are differentially expressed in childhood B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) and their potential roles in the progression of childhood ALL. METHODS: Microarrays were used to detect differentially expressed lncRNAs and mRNAs. Several aberrantly expressed lncRNAs were validated by qRT-PCR. Leukemia-free survival was analyzed using the Kaplan-Meier method with a log-rank test. The co-expression correlations of lncRNAs and mRNAs were determined by Spearman's correlation coefficient. CCK-8 assays and flow cytometry were performed to measure cell proliferation and apoptosis. RESULTS: We revealed that many lncRNAs were abnormally expressed in B-ALL and T-ALL. LncRNA/mRNA co-expression and the gene locus network showed that dysregulated lncRNAs are involved in diverse cellular processes. We also assessed the diagnostic value of the differentially expressed lncRNAs and confirmed the optimal combination of TCONS_00026679, uc002ubt.1, ENST00000411904, and ENST00000547644 with an area under the curve of 0.9686 [95 % CI: 0.9369-1.000, P < 0.001], with 90.7 % sensitivity and 92.19 % specificity, at a cut-off point of -0.5700 to distinguish childhood B-ALL patients from T-ALL patients, implying that these specific lncRNAs may have potential to detect subsets of childhood ALL. Notably, we found that the 8-year leukemia-free survival of patients with high TCONS_00026679 (p = 0.0081), ENST00000522339 (p = 0.0484), ENST00000499583 (p = 0.0381), ENST00000457217 (p = 0.0464), and ENST00000451368 (p = 0.0298) expression levels was significantly higher than that of patients with low expression levels of these lncRNAs, while patients with high uc002ubt.1 (p = 0.0499) and ENST00000547644 (p = 0.0451) expression levels exhibited markedly shorter 8-year leukemia-free survival. In addition, some lncRNAs were found to play different roles in cell proliferation and apoptosis in T-ALL and B-ALL. CONCLUSIONS: Dysregulated lncRNAs involved in different regulatory mechanisms underlying the progression of childhood T-ALL and B-ALL might serve as novel biomarkers to distinguish ALL subsets and indicate poor outcomes.

RNA sequencing: new technologies and applications in cancer research.

Over the past few decades, RNA sequencing has significantly progressed, becoming a paramount approach for transcriptome profiling. The revolution from bulk RNA sequencing to single-molecular, single-cell and spatial transcriptome approaches has enabled increasingly accurate, individual cell resolution incorporated with spatial information. Cancer, a major malignant and heterogeneous lethal disease, remains an enormous challenge in medical research and clinical treatment. As a vital tool, RNA sequencing has been utilized in many aspects of cancer research and therapy, including biomarker discovery and characterization of cancer heterogeneity and evolution, drug resistance, cancer immune microenvironment and immunotherapy, cancer neoantigens and so on. In this review, the latest studies on RNA sequencing technology and their applications in cancer are summarized, and future challenges and opportunities for RNA sequencing technology in cancer applications are discussed.

Antitubercular Ilamycins from Marine-Derived Streptomyces atratus SCSIO ZH16 ΔilaR.

Tuberculosis (TB) ranks as the leading cause of death from a single infectious agent (ranking more lethal than HIV/AIDS) over the course of the past decade. More concerning is that reports of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of TB have been dramatically increasing. It continues to become ever more clear that novel anti-TB drugs with improved efficacies and reduced toxicities are urgently needed. We report here the discovery of 12 new ilamycin analogues, ilamycins G-R (1-12), bearing various nonproteinogenic amino acids, along with ilamycins E1 (13) and F (14), from a 200 L scale culture of the marine-derived mutant actinomycete Streptomyces atratus SCSIO ZH16 ΔilaR. Importantly, bioassays against Mycobacterium tuberculosis H37Rv revealed that all 12 new agents displayed antitubercular activities with MIC values ranging from 0.0096 to 10 µM. The structures of 1-12 were elucidated on the basis of HRESIMS, 1D and 2D NMR, and X-ray single-crystal diffraction studies. In addition, compound 10 was found to be moderately cytotoxic against a panel of tumor human cell lines. From these data we can formulate tentative structure-activity relationships for the antitubercular and antitumor activities of the ilamycins.

Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis, and its treatment remains a challenge due to few targeted medicines and high risk of relapse, metastasis, and drug resistance. Thus, more effective drugs and new regimens for the therapy of TNBC are urgently needed. Ilamycins are a kind of cyclic peptides and produced by Streptomyces atratus and Streptomyces islandicus with effective anti-tuberculosis activity. Ilamycin C is a novel compound isolated from the deep South China Sea-derived Streptomyces atratus SCSIO ZH16 and exhibited a strong cytotoxic activity against several cancers including breast cancer cell line MCF7. However, the cytotoxic activity of Ilamycin C to TNBC cells and a detailed antitumor mechanism have not been reported. METHODS: CCK-8 assays were used to examine cell viability and cytotoxic activity of Ilamycin C to TNBC, non-TNBC MCF7, and nonmalignant MCF10A cells. EdU assays and flow cytometry were performed to assess cell proliferation and cell apoptosis. Transwell migration and Matrigel invasion assays were utilized to assess the migratory and invading capacity of TNBC cells following the treatment of Ilamycin C. The expressions of proteins were detected by western blot. RESULTS: In this study, we found that Ilamycin C has more preferential cytotoxicity in TNBC cells than non-TNBC MCF7 and nonmalignant MCF10A cells. Notably, our studies revealed the mechanism that Ilamycin C can induce Bax/Bcl-2-related caspase-dependent apoptosis and inhibit migration and invasion through MMP2/MMP9/vimentin/fascin in TNBC by suppressing IL-6-induced STAT3 phosphorylation. CONCLUSIONS: This study provides the first evidence that Ilamycin C has significant implications for the potential as a novel IL-6/STAT3 inhibitor for TNBC treatment in the future.

Natural products for treating colorectal cancer: A mechanistic review.

Colorectal cancer (CRC) is one of the most common types of cancers in humans and is closely linked to the global cancer-related mortalities worldwide. Molecular pathological epidemiology studies can reveal the risk factors of CRC and contribute to biomarker research and precision medicine. The current clinical treatment for CRC mainly involves surgery and chemotherapy. However, because of the occurrence of side effects and the emergence of drug resistance, there is an urgent need to find new and more effective drugs for CRC treatment. An increasing number of studies have demonstrated that many natural products possess effective anti-CRC effects and may serve as alternative chemotherapy agents for CRC treatment. In this review, we summarize the natural products with anti-CRC effects from different sources based on the chemical structures such as alkaloids, polysaccharides, polyphenols, terpenoid, unsaturated fatty acids, and discuss the natural product-derived drugs used clinically for colorectal cancer treatment. Furthermore, natural products of marine origin are also discussed for their enormous potential to serve as the candidate drugs. Notably, we generalize the experiment-based molecular mechanisms and the regulatory networks whereby natural products exert anticancer effects on cell proliferation, metastasis, apoptosis, autophagy, and angiogenesis.