The Emerging Role of LncRNA FENDRR in Multiple Cancers: A Review.

Long noncoding RNAs (lncRNAs) are prominent as crucial regulators of tumor establishment and are repeatedly dysregulated in multiple cancers. Therefore, lncRNAs have been identified to play an essential function in carcinogenesis and progression of cancer at genetic and epigenetic levels. FENDRR (fetal-lethal noncoding developmental regulatory RNA) as a LncRNA is a hallmark of various malignancies. FENDRR is crucial for multiple organs' development, such as the lung and heart. The effects of FENDRR under signaling pathways in different cancers have been identified. In addition, it has been verified that FENDRR can affect the development and progression of various cancers. In addition, FENDRR expression has been associated with epigenetic regulation of target genes participating in tumor immunity. Furthermore, FENDRR downregulation was observed in various types of cancers, including colorectal cancer, gastric cancer, pancreatic cancer, cholangiocarcinoma, liver cancer, gallbladder cancer, lung cancer, breast cancer, endometrial cancer, prostate cancer, chronic myeloid leukemia, osteosarcoma, and cutaneous malignant melanoma cells. Here, we review the biological functions and molecular mechanisms of FENDRR in several cancers, and we will discuss its potential as a cancer biomarker and as a probable option for cancer treatment.

Association between Glucose Consumption and Oocyte Maturation Competence in Mice with Polycystic Ovarian Syndrome.

BACKGROUND: This study evaluated association between glucose uptake by individually cultured oocyte and their maturation competence in mice with polycystic ovarian syndrome (PCOS). MATERIALS AND METHODS: In this experimental study, PCOS and non-PCOS cumulus-oocyte complexes (COCs), and cumulus-denuded oocytes (DOs) were cultured individually and categorized in four groups: i. PCOS DOs (n=83), ii. PCOS COCs (n=35), iii. Non-PCOS DOs (n=61) and iv. Non-PCOS COCs (n=62). After the culture period, 50 µl aliquots of the spent drops were used for glucose change analysis using high performance liquid chromatography. Polar NH2 column was used for the study of carbohydrates, acetonitrile with deionized water as the solvent phase and UV as detectors. Oocyte quality (growth differentiation factor 9: GDF-9), viability [bcl-2-like protein 4 (BAX) and B-cell lymphoma2 (BCL2)], in addition to fertilization and embryonic development rates were also evaluated in relation to glucose consumption rate of each oocyte. RESULTS: Maturation rate was significantly higher in non-PCOS COCs and DOs compared to PCOS COCs (IV: 70.9% vs. II: 45.71%) and DOs (III: 67.2% vs. 1: 53.01%), respectively. There was a significant negative correlation between high glucose intake (38.17 ppm) and BCL2 gene expression (P=0.03) in PCOS COCs compared to non-PCOS COCs. There was a significant difference in the GDF-9 gene expression from PCOS DOs (0.66 ± 0.02, P=0.003) and COCs (0.37 ± 0.02, P=0.0001) compared to non-PCOS DOs and COCs, respectively. A negative correlation was also observed between quality of PCOS-DOs and -COCs with glucose intake. Non-PCOS COCs significantly showed higher rate of successful IVF and development compared to PCOS COCs (P=0.01). CONCLUSION: Based on the importance of metabolic analysis, the glucose consumption by DOs and COCs in culture medium can be a suitable criterion for their quality assessment. So that, glucose consumption may reflect oocyte maturation competence.

TEffect of Single Embryo Blastomere Biopsy from Human Frozen Embryos on Assisted Reproductive Outcomes.

OBJECTIVE: Preimplantation genetic testing for aneuploidies (PGT-A) is used to determine chromosomal normality and achieve a successful live birth in infertile couples. There is a possible correlation between chromosomal aneuploidy, embryo development and pregnancy rate. This study evaluated the influence of single blastomere biopsy (SBB) on embryo development and pregnancy rates during frozen embryo transfer (FET) and fresh cycles. MATERIALS AND METHODS: This quasi-experimental study evaluated 115 intracytoplasmic sperm injection (ICSI) cycles, including 443 embryos (6-8 cells) with a grade A on day three, following PGT-A in the fresh or FET cycles from February 2018 to June 2020. In addition, the fresh cycles without PGT were included as a control group (n=166 embryos). SBB was done on day three and was grouped as FET-PGT (n=149) and the fresh-PGT (n=128). RESULTS: There is a more aneuploidy rate in the FET-PGT group compared to the fresh-PGT cycle (36.60% vs. 20.38%, P<0.001). There is a rate of higher development and blastocyst in the control group. While the embryos of PGT groups showed higher degrees of expansion (expansion 5) on day five. 8.6, 8.59, and 9.37% of expansion 3, 4, and 5 in the fresh-PGT embryos, 12.58, 2.78, and 14.84% of expansion 3, 4, and 5 in the FET-PGD embryos compared to 10.84and 33.73% of expansion 3 and 4 in the control group (without expansion 5; P<0.001). There was no significant relationship between 13, 18, and 21 chromosome aneuploidies with blastocyst development competence among the groups (P<0.1). Following embryo transfer (n=97), the spontaneous abortion rate was higher in the FET-PGT cycles compared to the fresh-PGT and control groups (50 vs. 22 and 11%, respectively; P<0.04). CONCLUSION: The process of SBB following vitrification significantly decreased embryo development and pregnancy outcomes. Therefore, a morphological analysis could not be reliable in selecting chromosomally normal embryos.

Metformin, clomiphene citrate and flutamide effects on oocyte ultrastructure status and quality in PCOS mouse model.

RESEARCH QUESTION: Polycystic ovary syndrome (PCOS) alters oocyte developmental competence and so the treatment of PCOS patients with assisted reproductive techniques is a major challenge for an infertility specialist. Does ovulation induction therapy with clomiphene citrate, metformin and flutamide affect abnormal PCOS follicle gene expression, its quality, and nuclear and cytoplasmic maturation in the oocyte matured in vitro? DESIGN: Fifty NMRI mice (7-8 weeks old) were randomly divided into five groups, including non-PCOS, PCOS and PCOS groups treated with clomiphene citrate (18 mg/kg body weight for 2 days), metformin (50 mg/100 g body weight for 30 days) and flutamide (10 mg/kg body weight injection for 15 days). The oocytes were collected for quantitative real-time polymerase chain reaction analysis (the evaluation of genes associated with oocyte maturation), transmission electron microscopy (the evaluation of cytoplasmic maturation) and in-vitro maturation (IVM) and IVF outcomes. RESULTS: The dysregulated expression of some genes of insulin-like growth factor (IGF) families involved in oocyte competence and steroid metabolism (e.g. Cyp19a1 and Cyp11a1), transforming growth factor beta (TGF-ß) family (e.g. Tgfb1, Gdf9, Bmp15, Inhbb and Bmpr1a), and oestrogen receptor signalling (e.g. Ncoa3, Pgr) was, to some extent, restored in the PCOS follicles following their with clomiphene citrate, metformin and flutamide. The improved cytoplasmic maturation was observed particularly in the PCOS mice treated with clomiphene citrate. The better IVM-IVF outcomes were also observed in the clomiphene citrate and metformin groups compared with the PCOS group. CONCLUSIONS: This study opens up a new perspective on knowing the effect of ovulation induction therapy on not only nuclear maturation but also ultrastructural characteristics, IVM-IVF outcomes and PCOS oocyte developmental competence.