Recurrent pregnancy loss (RPL) is a common complication in obstetrics, affecting about 5% of women of childbearing age. An increase in the number of abortions results in escalation in the risk of miscarriage. Although concentrated research has identified numerous causes for RPL, about 50% of them remain unexplained. Pregnancy is a complex process, comprising fertilization, implantation, organ and tissue differentiation, and fetal growth, which is effectively controlled by a number of both maternal and fetal factors. An example is the immune response, in which T cells and natural killer cells participate, and inflammation mediated by tumor necrosis factor or colony-stimulating factor, which hinders embryo implantation. Furthermore, vitamin D affects glucose metabolism and inhibits embryonic development, whereas microRNA has a negative effect on the gene expression of embryo implantation and development. This review examines the causes of RPL from multiple perspectives, and focuses on the numerous factors that may result in RPL.

Aim: To investigate the expression of FLNA and its potential prognostic significance in cervical cancer. Patients & methods: Real-time PCR was performed to evaluate the expression levels of FLNA in 44 pairs of cervical cancer and matched normal adjacent tissues. Kaplan–Meier analysis and Cox proportional hazards model were used to examine the correlation between FLNA expression levels and overall survival in cervical cancer patients. Results & conclusion: FLNA was significantly upregulated in cervical cancer tissues. FLNA expression level was associated with lymph node metastasis, parametrial invasion and response to neoadjuvant chemotherapy and predicted poor survival in cervical cancer patients. FLNA may serve as a predictor of chemosensitivity and a prognostic biomarker of survival in cervical cancer.

The ubiquitin–proteasome system (UPS) is responsible for proteasomal degradation, regulating the half-life of the protein. Deubiquitinating enzymes (DUBs) are components of the UPS and inhibit degradation by removing ubiquitins from protein substrates. Herpesvirus-associated ubiquitin-specific protease (HAUSP) is one such deubiquitinating enzyme and has been closely associated with tumor development. In a previous study, we isolated putative HAUSP binding substrates by two-dimensional electrophoresis (2-DE) and identified them by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF/MS) analysis. The analysis showed that pyruvate kinase isoenzyme M2 (PKM2) was likely to be one of the substrates for HAUSP. Further study revealed that PKM2 binds to HAUSP, confirming the interaction between these proteins, and that PKM2 possesses the putative HAUSP binding motif, E or P/AXXS. Therefore, we generated mutant forms of PKM2 S57A, S97A, and S346A, and found that S57A had less binding affinity. In a previous study, we demonstrated that PKM2 is regulated by the UPS, and that HAUSP- as a DUB-acted on PKM2, thus siRNA for HAUSP increases PKM2 ubiquitination. Our present study newly highlights the direct interaction between HAUSP and PKM2.

Octamer-binding transcription factor 3/4 (OCT-3/4), which is involved in the tumorigenesis of somatic cancers, has diverse functions during cancer development. Overexpression of OCT-3/4 has been detected in various human somatic tumors, indicating that OCT-3/4 activation may contribute to the development and progression of cancers. Stem cells can undergo self-renewal, pluripotency, and reprogramming with the help of at least four transcription factors, OCT-3/4, SRY box-containing gene 2 (SOX2), Krüppel-like factor 4 (KLF4), and c-MYC. Of these, OCT-3/4 plays a critical role in maintenance of undifferentiated state of embryonic stem cells (ESCs) and in production of induced pluripotent stem cells (iPSCs). Stem cells can undergo partitioning through mitosis and separate into specific cell types, three embryonic germ layers: the endoderm, the mesoderm, and the trophectoderm. It has been demonstrated that the stability of OCT-3/4 is mediated by the ubiquitin-proteasome system (UPS), which is one of the key cellular mechanisms for cellular homeostasis. The framework of the mechanism is simple, but the proteolytic machinery is complicated. Ubiquitination promotes protein degradation, and ubiquitination of OCT-3/4 leads to regulation of cellular proliferation and differentiation. Therefore, it is expected that OCT-3/4 may play a key role in proliferation and differentiation of proliferating cells.

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