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Bcl-x pre-mRNA splicing serves as a typical example to study the impact of alternative splicing in the modulation of cell death. Dysregulation of Bcl-x apoptotic isoforms caused by precarious equilibrium splicing is implicated in genesis and development of multiple human diseases, especially cancers. Exploring the mechanism of Bcl-x splicing and regulation has provided insight into the development of drugs that could contribute to sensitivity of cancer cells to death. On this basis, we review the multiple splicing patterns and structural characteristics of Bcl-x. Additionally, we outline the cis-regulatory elements, trans-acting factors as well as epigenetic modifications involved in the splicing regulation of Bcl-x. Furthermore, this review highlights aberrant splicing of Bcl-x involved in apoptosis evade, autophagy, metastasis, and therapy resistance of various cancer cells. Last, emphasis is given to the clinical role of targeting Bcl-x splicing correction in human cancer based on the splice-switching oligonucleotides, small molecular modulators and BH3 mimetics. Thus, it is highlighting significance of aberrant splicing isoforms of Bcl-x as targets for cancer therapy.

Poly (rC)-binding protein 1 (PCBP1), an RNA- or DNA-binding protein with a relative molecular weight of 38 kDa, which is characterized by downregulation in many cancer types. Numerous cases have indicated that PCBP1 could be considered as a tumor suppressor to inhibit tumorigenesis, development, and metastasis. In the current review, we described the multilevel regulatory roles of PCBP1, including gene transcription, alternative splicing, and translation of many cancer-related genes. Additionally, we also provided a brief overview about the inhibitory effect of PCBP1 on most common tumors. More importantly, we summarized the current research status about PCBP1 in hypoxic microenvironment, autophagy, apoptosis, and chemotherapy of cancer cells, aiming to clarify the molecular mechanisms of PCBP1 in cancer. Taken together, in-depth study of PCBP1 in cancer may provide new ideas for cancer therapy., (© 2020 Federation of American Societies for Experimental Biology.)

Transforming growth factor β (TGF-β) is part of the transforming growth factor β superfamily which is involved in many physiological processes and closely related to the carcinogenesis. Here, we discuss the TGF-β structure, function, and its canonical Smads signaling pathway. Importantly, TGF-β has been proved that it plays both tumor suppressor as well as an activator role in tumor progression. In an early stage, TGF-β inhibits cell proliferation and is involved in cell apoptosis. In an advanced tumor, TGF-β signaling pathway induces tumor invasion and metastasis through promoting angiogenesis, epithelial-mesenchymal transition, and immune escape. Furthermore, we are centered on updated research results into the inhibitors as drugs which have been studied in preclinical or clinical trials in tumor carcinogenesis to prevent the TGF-β synthesis and block its signaling pathways such as antibodies, antisense molecules, and small-molecule tyrosine kinase inhibitors. Thus, it is highlighting the crucial role of TGF-β in tumor therapy and may provide opportunities for the new antitumor strategies in patients with cancer., (© 2019 Wiley Periodicals, Inc.)

Pre-mRNA splicing is a fundamental process that plays a considerable role in generating protein diversity. Pre-mRNA splicing is also the key to the pathology of numerous diseases, especially cancers. In this review, we discuss how aberrant splicing isoforms precisely regulate three basic functional aspects in cancer: proliferation, metastasis and apoptosis. Importantly, clinical function of aberrant splicing isoforms is also discussed, in particular concerning drug resistance and radiosensitivity. Furthermore, this review discusses emerging strategies how to modulate pathologic aberrant splicing isoforms, which are attractive, novel therapeutic agents in cancer. Last we outline current and future directions of isoforms diagnostic methodologies reported so far in cancer. Thus, it is highlighting significance of aberrant splicing isoforms as markers for cancer and as targets for cancer therapy.

Exosomes are nanoscale vesicles shed from all cell types and play a major role in communication and transportation of materials between cells due to their ability to transfer proteins and nucleic acids from one cell to another. Analogous in size and function to synthetic nanoparticles, exosomes offer many advantages, rendering them the most promising candidates for targeted drug or gene delivery vehicles. Exosomes can also induce chemoresistance or radioresistance of tumor cells. Studies about the related mechanisms help overcome cancer therapy resistance to some extent. In this review, we focus on the application of exosomes as nanocarriers and the current status of the application of exosomes to cancer therapy.