MiR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine granulosa cells
JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY
Authors: Shi, Shengjie; Zhou, Xiaoge; Li, Jingjing; Zhang, Lutong; Hu, Yamei; Li, Yankun; Yang, Gongshe; Chu, Guiyan
Abstract
Background Granulosa cells (GCs) proliferation and estradiol synthesis significantly affect follicular development. The miR-214-3p expression in the ovarian tissues of high-yielding sows is higher than that in low-yielding sows, indicating that miR-214-3p may be involved in sow fertility. However, the functions and mechanisms of miR-214-3p on GCs are unclear. This study focuses on miR-214-3p in terms of the effects on GCs proliferation and estradiol synthesis. Results Our findings revealed that miR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine GCs. MiR-214-3p can increase the percentage of S-phase cells, the number of EdU labeled positive cells, and cell viability. However, E(2)concentration was reduced after miR-214-3p agomir treatment. We also found that miR-214-3p up-regulates the expression of cell cycle genes including cell cycle protein B (Cyclin B), cell cycle protein D (Cyclin D), cell cycle protein E (Cyclin E), and cyclin-dependent kinase 4 (CDK4) at the transcription and translation levels, but down-regulates the mRNA and protein levels of cytochrome P450 family 11 subfamily A member 1 (CYP11A1), cytochrome P450 family 19 subfamily A member 1 (CYP19A1), and steroidogenic acute regulatory protein (StAR) (i.e., the key enzymes in estradiol synthesis). On-line prediction, bioinformatics analysis, a luciferase reporter assay, RT-qPCR, and Western blot results showed that the target genes of miR-214-3p in proliferation and estradiol synthesis areMfn2andNR5A1, respectively. Conclusions Our findings suggest that miR-214-3p plays an important role in the functional regulation of porcine GCs and therefore may be a target gene for regulating follicular development.
Novel targeted therapies for metastatic breast cancer
ANNALS OF TRANSLATIONAL MEDICINE
Authors: Jazieh, Khalid; Bell, Ruth; Agarwal, Nayan; Abraham, Jame
Abstract
Metastatic breast cancer (mBC) continues to be a leading cause of cancer-related death in women. Even though mortality rates have improved over recent years, the 5-year survival rate of advanced BC is still at only 27%. As researchers and clinicians attempt to tackle this challenge, there has been extensive research and many trials studying treatment options for BC patients with metastatic disease, with numerous new therapies being discovered as a result. We review the most pertinent novel agents to enter the scope of BC treatment, including CDK4/6 inhibitors, PI3K inhibitors, mTOR inhibitors, immunotherapy, PARP inhibitors, and more.