Purpose It is known that microRNAs (miRNAs) are a class of small, noncoding RNAs that act as key regulators in various physiological and pathological processes. However, the regulatory mechanisms involving miRNAs in retinoblastoma (RB) remain largely unknown. The miRNA miR-125b is dysregulated in various human cancers such as breast cancer, human hepatocellular carcinoma, ovarian cancer, and colorectal cancer. However, the significance of miR-125b in RB has not been sufficiently investigated. Our objective was to explore the role of the miR-125b in RB. Methods In this study, we measured miR-125b levels using real-time polymerase chain reaction in human RB cell lines, including HXO-Rb44, Y79, SO-RB50, and the normal human retinal pigment epithelial cell line ARPE-19; a total of 38 pairs of primary RB tissues and adjacent noncancerous tissues were also measured. In addition, overexpression of miR-125b in RB cell lines was performed to determine the role of miR-125b in RB. Results We found that miR-125b is significantly upregulated in RB, and closely associated with tumor cell proliferation and apoptosis. In addition, overexpression of miR-125b apparently promotes RB cell proliferation and migration in vitro. Gain-offunction in vitro experiments further showed that the miR-125b mimic significantly suppressed RB cell apoptosis. A subsequent dual-luciferase reporter assay identified the suppressor gene DRAM2 as direct target of miR-125b.Conclusions Our data collectively demonstrate that miR-125b is a suppressor gene miRNA that can promote RB cell proliferation and migration by downregulating the suppressor gene DRAM2, indicating that miR-125b may represent a new potential diagnostic and therapeutic target for RB treatment.

Objective: MicroRNAs (miRNAs) are the most abundant small RNAs. Approximately annotated miRNAs genes have been found to be differentially expressed in ovarian follicles during the follicular development. Many miRNAs exert their regulatory effects on the apoptosis of follicular granulosa cells (FGCs) and follicular development (FD). However, accurate roles and mechanism of miRNAs regulating apoptosis of FGCs remain undetermined. Methods: In this review, we summarized the regulatory role of each miRNA or miRNA cluster on FGCs apoptosis and FD on the bases of 41 academic articles retrieved from PubMed and web of science and other databases. Results: Total of 30 miRNAs and 4 miRNAs clusters in 41 articles were reviewed and summarized in the present article. 29 documents indicated explicitly that 24 miRNAs and miRNAs clusters in 29 articles promoted or induced FGCs apoptosis through their distinctive target genes. The remaining 10 miRNAs and miRNAs of 12 articles inhibited FGCs apoptosis. were reported in all articles. MiRNAs exerted modulation actions by at least 77 signal pathways during FGCs apoptosis and FD. Conclusion: We concluded that miRNAs or miRNAs clusters could modulate the apoptosis of GCs (including follicular GCs, mural GCs and cumulus cells) by targeting their specific genes. A great majority of miRNAs show promoting role on apoptosis of FGCs in mammals. But the accurate mechanism of miRNAs and miRNA clusters has not been well understood. It is extremely necessary to ascertain clearly the role and mechanism of each miRNA or miRNA cluster in the future. Understanding precise functions and mechanisms of miRNAs in FGCs apoptosis and FD will be beneficial for finding new diagnostic and treatment strategy or scheme for infertility and ovarian diseases in humans and animals.

No abstract

No abstract

Experiments were conducted to determine if the follicle-stimulating hormone (FSH) receptor binding inhibitor (FRBI) impacts the expression levels of AT-rich interactive domain-containing protein 1A (ARID1A) and phosphatase and tensin homolog (PTEN) in ovaries and blood, as well as expressions of follicle-stimulating hormone cognate receptor (FSHR) gene and proteins. Mice in FRBI-10, FRBI-20, FRBI-30, and FRBI-40 groups were intramuscularly injected with 10, 20, 30, and 40 mg FRBI/kg, respectively, for five consecutive days. Western blotting and qRT-PCR were utilized to determine expression levels of ARID1A and PTEN proteins and mRNAs. Serum ARID1A and PTEN concentrations of the FRBI-40 group were higher than the control group (CG) and FSH group (P<0.05). FSHR mRNA levels of FRBI-20, FRBI-30, and FRBI-40 groups were lower than that of CG and FSH groups on day 15 (P<0.05 or P<0.01). Expression levels of FSHR proteins of FRBI-30 and FRBI-40 groups were lower than those of CG and FSH groups (P<0.05). Levels of ARID1A and PTEN proteins of the FRBI-30 group were greater than CG on days 20 and 30 (P<0.05). FRBI doses had significant positive correlations to levels of ARID1A and PTEN proteins. Additionally, ARID1A and PTEN had negative correlations to FSHR mRNAs and proteins. A high dose of FRBI could promote the expression levels of ARID1A and PTEN proteins in ovarian tissues. FRBI increased serum concentrations of ARID1A and PTEN. However, FRBI depressed expression levels of FSHR mRNAs and proteins in mouse ovaries.