Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis

Abstract

Background There is growing evidence discussing the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). We performed this study to explore the impact of exosomal lncRNA urothelial cancer-associated 1 (UCA1) in CC stem cells by sponging microRNA-122-5p (miR-122-5p) and regulating SOX2 expression. Methods CC stem cells (CD133+CaSki) and exosomes were extracted and identified. The synthesized UCA1- and miR-122-5p-related sequences were transfected into CaSki cells, CaSki cells-derived exosomes were extracted and then co-cultured with CD133+CaSki cells. The functional roles of UCA1 and miR-122-5p in self-renewal and differentiation ability of CC stem cells were determined using ectopic expression, knockdown/depletion and reporter assay experiments. An in vivo experiment was performed to verify the in vitro results. Results Up-regulated UCA1 and SOX2 and down-regulated miR-122-5p were found in CaSki-Exo. Exosomes promoted invasion, migration, proliferation and restrained apoptosis of CD133+CaSki cells. Silencing UCA1 or up-regulating miR-122-5p degraded SOX2 expression, and reduced invasion, migration and proliferation of CD133+CaSki cells while advanced apoptosis and suppressed the tumor volume and weight in nude mice. Conclusion Our study provides evidence that CaSki-Exo can promote the self-renewal and differentiation ability of CC stem cells while silencing UCA1 or up-regulating miR-122-5p restrains self-renewal and differentiation of CC stem cells.

Signaling by LncRNAs: Structure, Cellular Homeostasis, and Disease Pathology

“…LncRNA-Hh promotes sonic hedgehog–glioma-associated oncogene homolog 1 pathway to upregulate the expression of transcription factors, SRY-related HMG box transcription factor 2 (Sox-2) and octamer-binding transcription factor 4 (Oct-4), to enhance the self-renewal of cancer stem cells and mammosphere formation in breast cancers [ 138 ]. In cervical cancers, the elevated levels of UCA1 sequester miR-122-5p to upregulate Sox-2 expression, thereby facilitating cancer stemness [ 152 ]. LncRNA HOTAIR recruits PRC2 to the promoter of gene encoding miR-7 to induce repressive H3K27me3 methylation.…”

Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance

“…CAFs were shown to transfer lncRNA H19 to neighboring colorectal cancer cells [151,[160][161][162] and promote the stemness via activating Wnt/β-catenin signaling causing resistance to oxaliplatin-mediated apoptosis [163]. Exosomal lncRNA enhance invasion, migration, proliferation and inhibit apoptosis in cervical cancer cells and in NSCLC [164,165]. The importance of lncRNAs in regulating drug resistance in cancer cells has recently been described in a detailed review [166].…”

Predictive and Prognostic Value of Non-Coding RNA in Breast Cancer

“…Some exosomal lncRNAs can even mediate tumor microenvironment communication [ 40 ]. For example, exosomal lncRNA urothelial cancer-associated 1 (UCA1) enhances CD133+ cervical cancer cell differentiation and self-renewal via micro-rRNA-122-5P/SOX2 axis and UCA1 silencing leads to inhibited cell proliferation and invasion [ 41 ]. DOCK9-as2 is another exosomal lncRNA that decreases papillary thyroid carcinoma cell migration, epithelial-mesenchymal transition (EMT), and invasion when it is down-regulated [ 42 ].…”