IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer

Abstract

BackgroundEpithelial ovarian cancer (EOC) with insidious characteristic manifests no symptoms in its early onset but most patients have advanced and distant cancer metastasis at diagnosis. Innovative early diagnosis and effective treatment of EOC are urgently needed.MethodsIn the study, we developed a novel agent of IL-21-secreting human umbilical cord mesenchymal stem cells (hUCMSCs) combined with miR-200c to evaluate its effects on SKOV3 EOC in vitro and in vivo.ResultshUCMSCs-LV-IL-21 combined with miR-200c significantly inhibited the SKOV3 cell mobility and tumorigenesis compared with hUCMSCs-LV-IL-21, hUCMSCs-LV-vector, and hUCMSCs, respectively. These were reflected in decreasing the tumor sizes and elongating the tumor bearing nude mouse survival, accompanied with increasing the serum cytokine levels of IFN-γ, IL-21 and TNF-α as well as the splenocyte cytotoxicity. In addition, the expression of β-catenin, cyclin-D1, Gli1, Gli2, and ZEB1 was decreased but the E-cadherin expression was increased in tumor tissues of mice treated with hUCMSCs-LV-IL-21 plus miR-200c.ConclusionWe demonstrated that the synergistic effect of fighting SKOV3 EOC is attributable to repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in SKOV3 EOC. The findings may provide a new strategy for therapy of EOC.

Exosomes derived from microRNA-199a-overexpressing mesenchymal stem cells inhibit glioma progression by down-regulating AGAP2

“…Consistently, exosomes derived from MSCs that are modified by miR-122 are able to enhance the chemosensitivity of hepatocellular carcinoma as previously reported [36]. The combination of both miR-200c with IL-21-secreting human umbilical cord MSCs exerts an inhibitory role not only in the tumor growth and metastasis but also in the epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer [37].…”

Wnt Signaling in Ovarian Cancer Stemness, EMT, and Therapy Resistance

“…Several other miRs have been demonstrated to impact migration, invasion, and cancer progression via Wnt signaling in ovarian cancer [47,48,49,50,51,52,53,54,55,56,57,58,59]. Interestingly, miR-939 has been suggested to function as a tumor promotor by regulating Wnt signaling through direct suppression of the previously discussed APC2 tumor suppressor [48].…”

Interaction between LncRNA-ROR and miR-145 contributes to epithelial-mesenchymal transition of ovarian cancer cells

“…The five-year survival rate of patients with ovarian cancer is only 31% (Fidler 1978). Distant metastasis is a major cause of the poor survival of these patients (Rauh-Hain et al 2016;Tripathi et al 2018;Zhang et al 2018). Epithelial-mesenchymal transition (EMT) acts as a crucial role in embryonic development (Thiery 2003), and it has more recently been implicated in promoting carcinoma invasion and metastasis (Wang et al 2017).…”

“…Currently, many lncRNAs, except LncRNA-ROR, have been reported as key regulators of the occurrence and development of ovarian cancer (Zhang et al 2018). And LncRNA-ROR remains unknown in ovarian cancer progression and metastasis.…”