Novel targets in rectal cancer by considering lncRNA�miRNA�mRNA network in response to Lactobacillus acidophilus consumption: a randomized clinical trial

We aimed to explore the lncRNA�miR�mRNA network in response to Lactobacillusacidophilus (L. acidophilus) consumption in rectal cancer patients. The candidate miRs were first taken from the GEO and TCGA databases. We constructed the lncRNA�miR�mRNA network using the high-throughput sequencing data. At last, we created a heatmap based on the experimental data to show the possible correlation of the selected targets. The expression levels of selected targets were measured in the samples of 107 rectal cancer patients undergoing placebo and probiotic consumption and 10 noncancerous subjects using Real-Time PCR. Our analysis revealed a group of differentially expressed 12 miRs and 11 lncRNAs, and 12 genes in rectal cancer patients. A significant expression increase of the selected tumor suppressor miRs, lncRNAs, and genes and a substantial expression decrease of the selected oncomiRs, onco-lncRNAs, and oncogenes were obtained after the probiotic consumption compared to the placebo group. There is a strong correlation between some network components, including miR-133b and IGF1 gene, miR-548ac and MSH2 gene, and miR-21 and SMAD4 gene. In rectal cancer patients, L.acidophilus consumption was associated with improved expression of the lncRNA�miR�mRNA network, which may provide novel monitoring and therapeutic approaches. © 2022, The Author(s)

Role of oxytocin and c-Myc pathway in cardiac remodeling in neonatal rats undergoing cardiac apical resection

Oxytocin (OT) is a nonapeptide hormone that can improve cardiomyocyte proliferation, suggesting a potential heart regeneration function. Here, we investigated the role of oxytocin and the c-Myc pathway in cardiac remodeling in neonatal rats undergoing cardiac apical resection. We have utilized a knockout of oxytocin receptor (OTR) with OTR-shRNA. A neonatal rat model of cardiac resection (�10�15) was first established. The protein levels of OTR and c-Myc and the expression of cyclin d1 and c-Myc genes were then evaluated in the cardiac tissues at 1, 7, and 21 days after cardiac resection. We also analyzed the proliferation of cardiomyocytes through α-actinin, BrdU, and ki-67 markers. At last, the hemodynamic and electrophysiologic functions were evaluated eight weeks after cardiac resection. At 21 days, the regeneration of cardiomyocytes was repaired among rats in the control and resection groups, while OTR-shRNA groups were failed to improve. Inhibition of OTR failed cardiac regeneration and reduced the number of proliferating cardiomyocytes. The c-Myc protein was significantly reduced in the OTR-shRNA injection hearts. Moreover, we have severely found a depressed heart function in the OTR-shRNA injection animals. These observations revealed that the OT must improve cardiac remodeling in neonatal rat hearts by regulating the c-Myc pathway. © 2021 Elsevier B.V

An innovative systematic approach introduced the involved lncRNA-miR-mRNA network in cell cycle and proliferation after conventional treatments in breast cancer patients

The present study aimed to explore the involved lncRNA-miRNA-mRNA network in the cell cycle and proliferation after conventional treatments in Luminal A breast cancer patients.The candidate miRNAs (miRs), lncRNAs, and mRNAs were first taken from the Gene Expression Omnibus and TCGA databases. The lncRNA�miR�mRNA network was then constructed using the high-throughput sequencing data. The expression levels of selected targets were measured in the breast cancer and healthy samples by the Real-Time PCR technique and compared with the clinical outcomes by the Kaplan-Meier method.Our analysis revealed a group of differentially expressed 3 lncRNAs, 9 miRs, and 14 mRNAs in breast cancer patients. A significant expression decrease of the selected tumor suppressor lncRNAs, miRs, and genes and a substantial expression increase of the selected onco-lncRNAs, oncomiRs, and oncogenes were obtained in the patients compared to the healthy group. The plasma levels of the lncRNAs, miRs, and mRNAs were more significant after the operation, chemotherapy, and radiotherapy than the pre-treatment. The Kaplan-Meier analysis indicated that the patients with a high expression of miR-21, miR-20b, IGF1R, and E2F2 and a low expression of miR-125a, PDCD4, and PTEN had exhibited a shorter overall survival rate.Our results suggested that the underlying mechanisms of the lncRNA, miRs, and mRNAs and relevant signaling pathways may be considered predictive and therapeutic targets for breast cancer. © 2022 Informa UK Limited, trading as Taylor & Francis Group

Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs); where do they stand in tumorigenesis and how they can change the face of cancer therapy?

The tumor microenvironment (TME) and its components have recently attracted tremendous attention in cancer treatment strategies, as alongside the genetic and epigenetic alterations in tumor cells, TME could also provide a fertile background for malignant cells to survive and proliferate. Interestingly, TME plays a vital role in the mediation of cancer metastasis and drug resistance even against immunotherapeutic agents. Among different cells that are presenting in TME, tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) have shown to have significant value in the regulation of angiogenesis, tumor metastasis, and drug-resistance through manipulating the composition as well as the organization of extracellular matrix (ECM). Evidence has shown that the presence of both TAMs and CAFs in TME is associated with poor prognosis and failure of chemotherapeutic agents. It seems that these cells together with ECM form a shield around tumor cells to protect them from the toxic agents and even the adaptive arm of the immune system, which is responsible for tumor surveillance. Given this, targeting TAMs and CAFs seems to be an essential approach to potentiate the cytotoxic effects of anti-cancer agents, either conventional chemotherapeutic drugs or immunotherapies. In the present review, we aimed to take a deep look at the mechanobiology of CAFs and TAMs in tumor progression and to discuss the available therapeutic approaches for harnessing these cells in TME. © 202