RNA-binding protein (RBP) has a highly dynamic spatiotemporal regulation process and important biological functions. They are critical to maintain the transcriptome through post-transcriptionally controlling the processing and transportation of RNA, including regulating RNA splicing, polyadenylation, mRNA stability, mRNA localization, and translation. Alteration of each process will affect the RNA life cycle, produce abnormal protein phenotypes, and thus lead to the occurrence and development of tumors. Here, we summarize RBPs involved in tumor progression and the underlying molecular mechanisms whereby they are regulated and exert their effects. This analysis is an important step towards the comprehensive characterization of post-transcriptional gene regulation involved in tumor progression.

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RNA-binding proteins in tumor progression

The metastasizing mechanisms of lung cancer: Recent advances and therapeutic challenges

Lung cancer (LC) is the most common cancer-related death globally, and many efforts have been made to improve the patient care of LC patients, as well as the development of efficient methods and a wider range of biomarkers for prognosis, diagnosis, and treatment purposes. MicroRNAs (miRs, miRNAs) regulate a wide range of cellular functions and play a key role in the development and spreading of LC by inhibiting or degrading the expression of their target protein-coding genes. Because of their dysregulation and disruption in function, miRNAs have been linked to the malignant pathophysiology of LC by influencing many cellular functions involved in the disease. These biological processes include increased invasive and proliferative potential, cell cycle abnormality, apoptosis evasion, promotion of angiogenesis, EMT and metastasis, and reduced susceptibility to certain treatments. Here, we discuss the findings from recent years that show the role of oncogenic and TS miRNAs in LC, as well as their significance in LC pathogenesis, and resistance to anticancer therapy. We also explore the biological relevance of miRNAs and their clinical application in LC diagnosis and prognosis. 

A study of miRNAs as cornerstone in lung cancer pathogenesis and therapeutic resistance: A focus on signaling pathways interplay.

Therapeutic potential of AMPK signaling targeting in lung cancer: Advances, challenges and future prospects.

microRNAs (miRNAs), endogenous suppressors of target mRNAs, are deeply involved in every step of non-small cell lung cancer (NSCLC) development, from tumor initiation to progression and metastasis. They play roles in cell proliferation, apoptosis, angiogenesis, epithelial-to-mesenchymal transition, migration, invasion, and metastatic colonization, as well as immunosuppression. Due to their versatility, numerous attempts have been made to use miRNAs for clinical applications. miRNAs can be used as cancer subtype classifiers, diagnostic markers, drug-response predictors, prognostic markers, and therapeutic targets in NSCLC. Many challenges remain ahead of their actual clinical application; however, when achieved, the use of miRNAs in the clinic is expected to enable great progress in the diagnosis and treatment of patients with NSCLC.

https://www.mdpi.com/1422-0067/21/22/8782/pdf

Diagnostic and Therapeutic Implications of microRNAs in Non-Small Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases. The RNA binding protein, QKI, belongs to the STAR family and plays tumor-suppressive functions in NSCLC. QKI-5 is a major isoform of QKIs and is predominantly expressed in NSCLC. However, the underlying mechanisms of QKI-5 in NSCLC progression remain unclear. We found that QKI-5 regulated microRNA (miRNA), miR-196b-5p, and its expression was significantly up-regulated in NSCLC tissues. Up-regulated miR-196b-5p promotes lung cancer cell migration, proliferation, and cell cycle through directly targeting the tumor suppressors, GATA6 and TSPAN12. Both GATA6 and TSPAN12 expressions were down-regulated in NSCLC patient tissue samples and were negatively correlated with miR-196b-5p expression. Mouse xenograft models demonstrated that miR-196b-5p functions as a potent onco-miRNA, whereas TSPAN12 functions as a tumor suppressor in NSCLC in vivo. QKI-5 bound to miR-196b-5p and influenced its stability, resulting in up-regulated miR-196b-5p expression in NSCLC. Further analysis showed that hypomethylation in the promoter region enhanced miR-196b-5p expression in NSCLC. Our findings indicate that QKI-5 may exhibit novel anticancer mechanisms by regulating miRNA in NSCLC, and targeting the QKI5∼miR-196b-5p∼GATA6/TSPAN12 pathway may enable effectively treating some NSCLCs.

https://www.pnas.org/content/pnas/117/8/4347.full.pdf

Yumin Wang

Papers

miR-196b-5p–mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer