Colorectal cancer (CRC) is a heterogeneous malignancy leading to increased mortality and poor prognosis due to the lack of efficient early diagnostics. Metastasis of the tumor being the most common cause of mortality is accountable for almost 90% of CRC associated deaths. Intensified screening procedures and molecular target identification has inflated the median survival rate of in CRC patients. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have come forward as potential targets for developing a novel approach in CRC theragnostics. Non-coding RNA (ncRNAs) sequences are abundantly present and thereby play a vital role in several biological processes such as cellular organization, cell fate determination, proliferation, apoptosis, tissue homeostasis maintenance as well as pathological conditions such as cancer by acting as post transcriptional regulators of gene expression. Several studies have highlighted the involvement of these ncRNAs in CRC development. However, the molecular mechanism involved in regulating CRC has not been clearly elucidated. This review, throws light upon the several non-coding RNAs involved in CRC with a focus on novel mechanisms of action, recent advances in the regulatory mechanisms that control the gene expression related to carcinogenesis. Furthermore, the potential role of ncRNAs as diagnostic as well as therapeutic targets has been reviewed.

Background: The mesenchymal stem cells (MSCs) have enormous therapeutic potential owing to their multi-lineage differentiation and self-renewal properties. MSCs express growth factors, cytokines, chemokines, and non-coding regulatory RNAs with immunosuppressive, anti-tumor, and migratory properties. MSCs also release several anti-cancer molecules via extracellular vesicles, that act as pro-apoptotic/tumor suppressor factors. This study aimed to identify the stem cell-derived secretome that could exhibit anti-cancer properties through molecular profiling of cargos in MSC-derived exosomes. Methods: Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from umbilical cord tissues and culture expanded. Subsequently, exosomes were isolated from hUCMSC conditioned medium and characterized by DLS, electron microscopy. Western blot for exosome surface marker protein CD63 expression was performed. The miRNA profiling of hUCMSCs and hUCMSC-derived exosomes was performed, followed by functional enrichment analysis. Results: The tri-lineage differentiation potential, fibroblastic morphology, and strong expression of pluripotency genes indicated that isolated fibroblasts are MSCs. The isolated extracellular vesicles were 133.8 ± 42.49 nm in diameter, monodispersed, and strongly expressed the exosome surface marker protein CD63. The miRNA expression profile and gene ontology (GO) depicted the differential expression patterns of high and less-expressed miRNAs that are crucial to be involved in the regulation of apoptosis. The LCMS/MS data and GO analysis indicate that hUCMSC secretomes are involved in several oncogenic and inflammatory signaling cascades. Conclusion: Primary human MSCs released miRNAs and growth factors via exosomes that are increasingly implicated in intercellular communications, and hUCMSC-exosomal miRNAs have a critical influence in regulating cell death and apoptosis of cancer cells. Graphical abstract

No abstract

Colon cancer etiology involves a wide spectrum of genetic and epigenetic alterations, finding it challenging to find effective therapeutic strategies. Quercetin exhibits potent anti-proliferative/apoptotic properties. In the present study, we aimed to elucidate the anti-cancer and anti-aging effect of quercetin in colon cancer cell lines. The anti-proliferative effect of quercetin was assessed in vitro by CCK-8 in normal and colon cancer cell lines. To check the anti-aging potential of quercetin, collagenase, elastase, and hyaluronidase inhibitory activity assays were performed. The epigenetic and DNA damage assays were performed using the human NAD-dependent deacetylase Sirtuin-6, proteasome 20S, Klotho, Cytochrome-C, and telomerase ELISA kits. Furthermore, the aging-associated miRNA expression profiling was performed on colon cancer cells. The treatment with quercetin inhibited cell proliferation of colon cancer cells in a dose-dependent manner. Quercetin arrested colon cancer cell growth by modulating expression of aging proteins including Sirtuin-6 and Klotho and also by inhibiting telomerase activity to restrict the telomere length which is evident from qPCR analysis. Quercetin also exhibited DNA damage protection by reducing proteasome 20S levels. The miRNA expression profiling results displayed differential expression of miRNA in colon cancer cell, and in addition, the highly upregulated miRNA was involved in the regulation of cell cycle, proliferation, and transcription. Our data suggest that quercetin treatment inhibited cell proliferation in colon cancer cells through regulating the anti-aging protein expression and provides better understanding for quercetin’s potential use in colon cancer treatment.

Background: Rhodiola rosea, an herb which has been used in traditional medicine for several years and LF, a class of lipoproteins, derived from the fish Trachurus sp. (LF-T) exhibits known anti-inflammatory activity. Objective: Investigating the anti-aging effect of Rhodiola Specific Bioactive Fractions cluster in combination with LF-T (R-L compound) in H2O2 mediated oxidative stress induced human amnion derived epithelial cell line - FL cells. Methods: FL cells treated with H2O2 to induce cellular aging, followed by treatment of R-L compound to study its antiaging characteristics. Based on the proliferation rate, 0.05% and 0.1% concentration of R-L compound was determined using MTT assay. Anti-aging and anti-oxidant assays – ABTS, DPPH, Hyaluronidase activity Nitric Oxide, Lipid Peroxidase and Superoxide Dismutase were performed. qPCR for anti-aging genes and matrix metalloproteinase genes were analyzed. Results: FL cells treated with R-L compound exhibited with increased proliferation rate and free-radical reduction. Decreased Hyaluronidase enzyme activity and regulation of genes such as SIRT1, KLOTHO, SERPINA 6, MMP 9 and MMP 2 expression depicts the anti-aging role of R-L compound. Chemometric profiling of the R-L compound revealed that aromatic compounds and unsaturated fatty acids along with their derivatives were present predominantly which might have attributed for the potent oxidative stress impeded aging activity. Conclusion: Specific Bioactive Fractions of Rhodiola in combination with LF-T obtained from Trachurus sp. involves in the regulation of aging genes and might be a novel approach to prevent the cells from oxidative stress damage and also it might avert the aging of cells.