Cellular communication can be mediated by the exchange of biological information, mainly in the form of proteins and RNAs. This can occur when extracellular vesicles, such as exosomes, secreted by a donor cell are internalized by an acceptor cell. Exosomes bear specific repertoires of proteins and RNAs, indicating the existence of mechanisms that control the sorting of molecules into them. Knowledge about loadings and processes and mechanisms of cargo sorting of exosomes is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. In this review, we will discuss the molecular mechanisms associated with exosome secretion and their specific cargo sorting, with special attention to the sorting of RNAs and proteins, and thus the outcome and the emerging therapeutic opportunities of the communication between the exosome-producer and recipient cells.

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Chemoresistance is a severe outcome among patients with epithelial ovarian cancer (EOC) that leads to a poor prognosis. YBX-1 has been shown to cause treatment failure and cancer progression in EOC. However, strategies that directly target YBX-1 are not yet conceivable. Here, we identified that SIAH1 which was downregulated in chemoresistant EOC samples and cell lines functioned as novel E3 ligases to trigger degradation of YBX-1 at cytoplasm by RING finger domain. Mechanistic studies show that YBX-1 was ubiquitinated by SIAH1 at lys304 that lead to the instability of its target m5C-modified mRNAs, thus sensitized EOC cells to cDDP. Overexpression of SIAH1 enhanced the antitumor efficacy of cisplatin in vitro and in vivo, which were partially impaired by ectopic expression of YBX-1 or depletion of YBX-1 ubiquitination. In summary, our data identify the SIAH1/YBX-1 interaction as a therapeutic target for overcoming EOC chemoresistance.

Premature ovarian failure (POF) is a common disease in women, characterized as abnormal declines in ovarian follicle numbers and oocyte quality. Patients have early depletion of primordial follicle pool associated with amenorrhea before the age of 40, which could be diagnosed by elevated serum FSH levels (>40 IU/L). 1,2 Causes of this disease could be mitochondrial dysfunction, auto-immune, chemotherapeutic treatments and cell senescence. 3 During ageing and senescence, accumulation of endogenous reactive oxygen species (ROS) and weakened antioxidant defences promoted oxidative damage in cell structures, rendering membranal lipid peroxidation, enzyme inactivation, protein oxidation and DNA damage. 4,5 As stated in the widely acknowledged 'free radical theory', oxidative damage continuously occurs during ageing and ROS is the driving force of ageing and cell senescence, whereas ageing is also a result of oxidative damage. 6,7 In addition, crosstalk between oocytes and GCs regulates oocytes competency and female fertility, deciding