In order to develop an improved anti-miR therapeutic agent for the treatment of ovarian cancer, a nanoformulation is engineered that leverages biodegradable porous silicon nanoparticles (pSiNPs) encapsulating an anti-miR-21 locked nucleic acid payload and displaying a tumor-homing peptide for targeted distribution.
In addition, Wnt signaling pathway inhibitors and activators were used to validate the hypothesis that the miR‑21/Wnt/CD44v6 pathway plays an important role in OC.
Functional studies reveal that miR21 is transferred from CAAs or CAFs to the cancer cells, where it suppresses ovarian cancer apoptosis and confers chemoresistance by binding to its direct novel target, APAF1.
Notably, reduced expression of miRNA‑21 replicated the effect of celastrol on OVCAR3 cells and inhibited the PI3K/p‑Akt‑NF‑κB signaling pathway in an in vitro model of ovarian carcinoma.
Gene set enrichment analysis on averaged ProMISe uniquely revealed respective target enrichments of oncomirs miR-21 and 145 in glioblastoma and ovarian cancers.
Berberine could inhibit miR-21 expression and function in ovarian cancer, as shown by an enhancement of its target PDCD4, an important tumor suppressor in ovarian cancer.
In total, 65 microRNAs were identified to exhibit differential expression in either LHR expressing SKOV3 cells or LH-treated cells, a few of which have been found in the genomic fragile regions that are associated with abnormal deletion or amplification in cancer, such as miR-21, miR-101-1, miR-210 and miR-301a.