An increasing number of studies have demonstrated that circular RNAs (circRNAs) can regulate gene expression through interacting with microRNAs. In this study, we analyzed the expression of antisense to CDR1as in colorectal cancer (CRC). CDR1as had a higher expression in CRC tissues compared to adjacent, normal mucosa and was positively associated with tumor size, T stage, lymph node metastasis, and poor overall survival (OS). Downregulation of CDR1as suppressed CRC cell proliferation and invasion and increased microRNA-7 (miR-7) expression. Intriguingly, ectopic expression of miR-7 in CRC cells consistently inhibited proliferation and invasion, and the miR-7 inhibitor was able to rescue the function of CDR1as knockdown. Mechanistic studies demonstrated that CDR1as silencing suppressed EGFR and IGF-1R expression, which could be partially blocked by the miR-7 inhibitor. Finally, positive correlations between CDR1as expression and EGFR and IGF-1R expression were observed in CRC samples. Thus, given the importance of CDR1as in blocking miR-7 and positively regulating EGFR and IGF-1R, dysregulated CDR1as expression may play an important role in CRC progression.

Some studies have shown that long-term gonadotropin-releasing hormone (GnRH) agonist administration before in vitro fertilization/intracytoplasmic sperm in infertile women with endometriosis or adenomyosis significantly increases the chances of pregnancy. We were interested in whether long-term GnRH agonist pretreatment could improve pregnancy outcomes in adenomyosis patients undergoing frozen embryo transfer (FET) after preparation of the endometrium with hormone replacement therapy (HRT). Totally, 339 patients with adenomyosis were included in this retrospective study, 194 received long-term GnRH agonist plus HRT (down-regulation + HRT) and 145 received HRT. There were no differences between the groups in characteristic such as age, body mass index, duration or cause of infertility, serum CA-125 level and basal hormone levels. On the day of progesterone administration, mean endometrial thickness and serum progesterone level were significantly greater in HRT patients. Mean score and number of embryos transferred showed no differences. In down regulation + HRT group, clinical pregnancy, implantation and ongoing pregnancy rates were 51.35%, 32.56% and 48.91%, respectively, significantly higher than that of HRT group (24.83%, 16.07% and 21.38%, respectively). So, we concluded that in FET, long-term GnRH agonist pretreatment significantly improved pregnancy outcomes in patients with adenomyosis.

SUMMARY Myeloid-biased hematopoietic stem cells (MB-HSCs) play critical roles in recovery from injury, but little is known about how they are regulated within the bone marrow niche. Here, we describe an auto/paracrine physiologic circuit that controls quiescence of MB-HSCs and hematopoietic progenitors marked by histidine decarboxylase (Hdc). Committed Hdc+ myeloid cells lie in close anatomical proximity to MB-HSCs and produce histamine, which activates the H2 receptor on MB-HSCs to promote their quiescence and self-renewal. Depleting histamine-producing cells enforces cell cycle entry, induces loss of serial transplant capacity, and sensitizes animals to chemotherapeutic injury. Increasing demand for myeloid cells via LPS treatment specifically recruits MB-HSCs and progenitors into the cell cycle; cycling MB-HSCs fail to revert into quiescence in the absence of histamine feedback, leading to their depletion, while an H2 agonist protects MB-HSCs from depletion after sepsis. Thus, histamine couples lineage-specific physiological demands to intrinsically-primed MB-HSCs to enforce homeostasis.