N6-methyladenosine modification is the most common RNA modification mechanism in mammals. YTHDF1, a m⁶A reader, can recognize the m⁶A of mRNAs to facilitate the interaction with the mRNA ribosome assembly and recruitment of translation initiators to promote translation. From a clinical perspective, YTHDF1 upregulation is frequently observed in breast cancer, but its involvement in those cancer-related events is still unclear. Here we report that YTHDF1 is a cancer driver capable of facilitating the proliferation and invasion of breast cancer cells as well as enhancing tumorigenicity and metastasis through promoting glycolysis. We found that tumor hypoxia can transcriptionally induce HIF1α and post-transcriptionally inhibit the expression of miR-16-5p to promote YTHDF1 expression, which could sequentially enhance tumor glycolysis by upregulating PKM2 and eventually increase the tumorigenesis and metastasis potential of breast cancer cells. Inhibiting YTHDF1 via gene knockdown or miR-16-5p would significantly abolish YTHDF1-dependent tumor growth and metastasis. In summary, we identified the role of the YTHDF1-PKM2 signal axis in the occurrence and development of breast cancer, which can be used as a potential target for breast cancer treatment.

Gastric cancer (GC) is one of the most common cancers, with high incidences in East Asia. microRNAs (miRNAs) play essential roles in the carcinogenesis of GC. miR-20a was elevated in GC, while the potential function of miR-20a was poorly understood. miR-20a expression was examined in GC tissues and cell lines. The effects of miR-20a on the growth, migration, invasion, and chemoresistance of GC cells were examined. Luciferase reporter assay and Western blot were used to screen the target of miR-20a. miR-20a was increased in GC tissues and cell lines. miR-20a promoted the growth, migration and invasion of GC cells, enhanced the chemoresistance of GC cells to cisplatin and docetaxel. Luciferase activity and Western blot confirmed that miR-20a negatively regulated EGR2 expression. Overexpression of EGR2 significantly attenuated the oncogenic effect of miR-20a. miR-20a was involved in the carcinogenesis of GC through modulation of the EGR2 signaling pathway.

Identification of the recombination hot/cold spots is critical for understanding the mechanism of recombination as well as the genome evolution process. However, experimental identification of recombination spots is both time-consuming and costly. Developing an accurate and automated method for reliably and quickly identifying recombination spots is thus urgently needed.

Osteoporosis is a global health concern arising from estrogen deficiency, intestinal dysbiosis, and dysregulation of the bone immune system. The absence of

Membrane transport proteins and their substrate specificities play crucial roles in a variety of cellular functions. Identifying the substrate specificities of membrane transport proteins is closely related to the protein-target interaction prediction, drug design, membrane recruitment, and dysregulation analysis. However, experimental methods to this aim are time consuming, labor intensive, and costly. Therefore, we proposed a novel method basing on support vector machine (SVM) to predict substrate specificities of membrane transport proteins by integrating features from position-specific score matrix (PSSM), PROFEAT, and Gene Ontology (GO). Finally, jackknife cross-validation tests were adopted on a benchmark and independent datasets to measure the performance of the proposed method. The overall accuracy of 96.16 and 80.45 percent were obtained for two datasets, which are higher (from 2.12 to 20.44 percent) than that by the state-of-the-art tool. Comparison results indicate that the proposed model is more reliable and efficient for accurate prediction the substrate specificities of membrane transport proteins.