miR-18a-5p derived from mesenchymal stem cells-extracellular vesicles inhibits ovarian cancer cell proliferation, migration, invasion, and chemotherapy resistance

Abstract

Objective Ovarian cancer (OC) is a major threat to women’s health. Mesenchymal stem cells (MSCs) are key regulators in cellular communication by secreting extracellular vesicles (EVs) that are involved in OC. This study probed into the mechanism of human MSCs derived-EVs (hMSC-EVs) in regulating OC cell growth and chemotherapy resistance. Methods hMSCs and EVs were isolated and identified. After adding EVs, the uptake of EVs by OC CAOV3/ES2 cells (for in vitro studies), and cell proliferation, migration, and invasion were detected. Downregulated miRNAs in hMSC-EVs were screened and miR-18a-5p expression in OC patients was detected. The prognosis of OC patients was analyzed. Binding sites of miR-18a-5p and NACC1 were predicted and validated. NACC1 expression in OC tissues was measured by RT-qPCR, and its correlation with miR-18a-5p was analyzed by Pearson method. AKT/mTOR pathway activation was assessed by WB. The cisplatin sensitivity of EVs-treated CAOV3 cells was evaluated via MTT assay and tested by tumor formation assay in nude mice. Results hMSC-EVs suppressed OC cell proliferation, migration, and invasion. miR-18a-5p was downregulated in OC and miR-18a-5p low expression was associated with a poor prognosis. EV-encapsulated miR-18a-5p targeted NACC1. NACC1 was upregulated in OC tissues. miR-18a-5p knockdown and NACC1 overexpression both annulled the inhibition of hMSC-EVs on OC cell growth. AKT and mTOR were elevated in OC and NACC1 activated the AKT/mTOR pathway in OC cells. hMSC-EVs promoted cisplatin sensitivity of OC cells by carrying miR-18a-5p. Conclusion hMSC-EVs-derived miR-18a-5p inhibits OC cell proliferation, migration, invasion, and chemotherapy resistance.

Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatment

“…However, it remains unclear what role each member of the cluster plays in tumorigenesis. For miR‐18a, both an oncogenic and tumor suppressive function is discussed 34,36,53–63 . In the migration and invasion assays on the mCRC cell line LIM2099, we aimed to investigate the effect of miR‐18a on tumor carcinogenesis.…”

miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach

“…Although there are published data describing the oncogenic [ 52 ] role of miR18a-5p, other studies have suggested a key tumor suppressor [ 53 , 54 ] function of this miRNA in several types of cancers, including ovarian cancers [ 54 ]. As such, in vitro overexpression of miR-18a-5p improved overall survival in an animal model of lung cancer by increasing radiosensitivity of lung cells and inhibiting the development of A549 xenografts after radiation treatment [ 55 ].…”

Mesenchymal stromal/stem cell-derived exosomes and genitourinary cancers: A mini review

“…Additionally, mature MSCs play a crucial role in cell signaling as important tumor-targeted conveyance agents by depositing EVs that are highly enriched with miRNAs ( O'Brien et al, 2018 ). In terms of the most prevalent malignancies that result in mortality, OCa is in eighth place ( Webb and Jordan, 2017 ; Wang et al, 2022 ).…”