Pimaric acid is a naturally occurring resin and has been found to perform many pharmacological activities including, anticancer activity. However, the role of Pimaric acid in ovarian cancer is still not known. This investigation aimed to evaluate the anticancer effects of Pimaric acid and its molecular mechanism in human ovarian cancer cells. MTT assay was used to examine cell viability. Cell morphology was determined through phase contrast microscopy. DAPI staining and TUNEL assay were performed for apoptotic study. Examination of cell cycle phase distribution was carried out through flow cytometry. In vitro wound healing assay was used for cell migration determination. Pimaric acid induced cytotoxicity in human ovarian cancer cells (PA-1) in a dose-dependent manner without causing too much cytotoxicity in human ovarian epithelial cells (T1074). Cell morphology in treated cancer cells showed significant changes compared to untreated controls. Furthermore, it was observed that the cytotoxic effects of Pimaric acid were apoptosis-mediated and caspase-dependent cascade. Western blotting analysis showed that the expression of apoptosis-associated proteins like BAX, p-53 and caspase-3 was enhanced and BCL-2 expression was diminished. The induction of cytotoxicity was mediated via endoplasmic reticulum stress through expressions of related proteins which showed a tremendous increase in p-PERK, PERK, AT-4, CHOP and IRE-1 levels after treatment. Cell cycle analysis through cytometry showed significant results as it revealed G2/M phase cell cycle arrest. Furthermore, the in vitro wound healing assay showed specific anti-migratory effects of Pimaric acid on PA-1 cells. In conclusion it can be assumed that Pimaric acid may act as a potential anticancer agent against ovarian carcinoma, however further investigations are required to validate this initial claim.

Recurrent implantation failure (RIF) is attributed to endometrial receptivity dysfunction with many unanswered questions. Up to now, there is no explanation for RIF, and therapeutic strategies are usually limited to supportive care. In this study, we differentially analyzed the raw data deposited in three eligible microarray datasets, GSE111974, GSE121219, and GSE147442 to screen DE-mRNAs, DE-miRNAs, and DE-circRNAs, respectively. The value of log2-fold change |log2FC| ≥ 1 and the adjusted p value < 0.05 were considered differentially expressed between RIF and fertile control. We found 350 DE-mRNAs, 43 DE-miRNAs, and 1968 DE-circRNAs between RIF and fertile control. The PPI network identified 6 hub genes with degree ≥10, KDR, AGT, POSTN, TOP2A, RRM2, and PTGS2, in RIF. KDR, AGT, POSTN, TOP2A, and RRM2 were downregulated in endometrial tissue samples of RIF compared with those of fertile control, while PTGS2 was upregulated in endometrial tissue samples of RIF compared with those of fertile control. According to the ceRNA hypothesis, 15 groups of ceRNA network based on 10 circRNAs, hsa_circ_001572, hsa_circ_001884, hsa_circ_001375, hsa_circ_001449, hsa_circ_000029, hsa_circ_001168, hsa_circ_000210, hsa_circ_001484, hsa_circ_001698, and hsa_circ_000089 were constructed in RIF. In conclusion, the present study examined the possible role of circRNAs and their related ceRNA network involved in the pathogenesis of RIF.