Min Zhao

Placenta-derived trophoblast extracellular vesicles contain unique miRNAs that inhibit ovarian cancer cell growth

Abstract Previous reports have indicated that placental trophoblast extracellular vesicles (EVs) possess unique properties that enable them significantly to inhibit the proliferation of ovarian cancer cells in vitro and slow ovarian tumour growth in an in vivo model, while EVs derived from monocytes did not. However, the mechanisms underlying the inhibitory effects of trophoblast EVs remain unclear. In this study, we characterized the microRNAs (miRNAs) uniquely present in placental trophoblast EVs but absent from THP-1 monocyte-derived EVs. Through bioinformatic analysis, we elucidated the potential involvement of these unique miRNAs in the negative regulation of proliferation pathways implicated in ovarian cancer. Functional assays demonstrated that placental trophoblast EVs inhibited ovarian cancer cell proliferation, and this effect was reversed upon blocking EV uptake, indicating the transfer of the contents of the EVs as a crucial mechanism modulating cancer cell viability. Using miRNA mimics, we also demonstrated that specific miRNAs from placental trophoblast EVs exhibited inhibitory effects on ovarian cancer cell proliferation, highlighting the potential of placental trophoblast EVs as therapeutic agents. These findings not only shed light on the molecular mechanisms underlying the therapeutic efficacy of placental trophoblast EVs but also provide valuable insights into the potential development of miRNA-based therapies for ovarian cancer, including the use of trophoblast EVs as a therapeutic for ovarian cancer.

Understanding How Pregnancy Protects Against Ovarian and Endometrial Cancer Development: Fetal Antigens May Be Involved

AbstractIt is well known that many factors, including infertility, obesity, type 2 diabetes, and family history of cancer, increase the risk of developing endometrial and ovarian cancer. However, multiparous women are known to have a lower risk of developing either ovarian or endometrial cancer than nonparous women. The lack of ovulation and shifting of sex hormonal balance, with decreased estrogen levels and increased progesterone levels during pregnancy, has traditionally been thought to be the major contributor to this decreased risk. However, in reality, the mechanisms underlying this phenomenon are relatively unknown. Increasing evidence suggests that endocrine factors are unlikely to completely explain the protective effect of pregnancies, and that multiple other nonendocrine mechanisms including fetal antigens and the newly proposed dormant cells hypothesis may also be involved. In this review, we summarize recent evidence and describe the potential underlying mechanisms that may explain how pregnancy protects against the development of ovarian and endometrial cancers in women's later life.

LINC01089 inhibits the progression of cervical cancer via inhibiting miR‐27a‐3p and increasing BTG2

AbstractBackgroundIncreasing evidence confirms that long non‐coding RNA (lncRNA) has a vital impact on the procession of cervical cancer (CC). The present study aimed to investigate the clinical significance of LINC01089 in CC, as well as explore its biological functions and potential molecular mechanisms.MethodsA quantitative real‐time polymerase chain reaction (qRT‐PCR) was utilized to investigate the expression of LINC01089 and miR‐27a‐3p in CC cells and tissues. Analysis of the correlation between the expression level of LINC01089 and the clinical pathological parameters of CC was then conducted. The human CC cell lines HeLa and SiHa were utilized for transfection to establish a gain‐of‐function model and loss‐of‐function models. Western blotting and a qRT‐PCR were performed to detect B‐cell translocation gene‐2 (BTG2) expression in CC cells. Cell counting kit (CCK)‐8 and 5‐bromo‐2‐deoxyuridine (BrdU) assays were performed to detect the proliferation of CC cells. The transwell method was employed to evaluate the migration and invasion of CC cells. The interactions between LINC01089 and miR‐27a‐3p were verified by bioinformatics, a dual luciferase reporter gene experiment and a RNA immunoprecipitation experiment, respectively.ResultsThe expression of LINC01089 in CC was markedly down‐regulated. The low expression of LINC01089 in CC was closely associated with a larger tumor size and positive lymph node metastasis. Moreover, overexpression of LINC01089 impeded the proliferation and metastasis of CC cells, whereas knockdown of LINC01089 had the opposite biological functions. In terms of mechanism, LINC01089 could sponge miR‐27a‐3p and indirectly up‐regulate BTG2 expression.ConclusionsLINC01089, as a tumor suppressor, impedes the development of CC by targeting miR‐27a‐3p to up‐regulate BTG2 expression.