Interplay within tumor microenvironment orchestrates neoplastic RNA metabolism and transcriptome diversity. (9th June 2021)

• Record Type: Journal Article
• Authors: Natua, Subhashis; Dhamdhere, Shruti Ganesh; Mutnuru, Srinivas Abhishek; Shukla, Sanjeev
• Is Part Of: Wiley interdisciplinary reviews. Volume 13:Number 2(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-06-09
• Subjects: extracellular vesicles -- hypoxia -- RNA metabolism -- RNA processing -- tumor microenvironment; RNA -- Periodicals; 572.8805
• DOI: 10.1002/wrna.1676
• Languages: English
• ISSNs: 1757-7004

Abstract

Abstract: The heterogeneous population of cancer cells within a tumor mass interacts intricately with the multifaceted aspects of the surrounding microenvironment. The reciprocal crosstalk between cancer cells and the tumor microenvironment (TME) shapes the cancer pathophysiome in a way that renders it uniquely suited for immune tolerance, angiogenesis, metastasis, and therapy resistance. This dynamic interaction involves a dramatic reconstruction of the transcriptomic landscape of tumors by altering the synthesis, modifications, stability, and processing of gene readouts. In this review, we categorically evaluate the influence of TME components, encompassing a myriad of resident and infiltrating cells, signaling molecules, extracellular vesicles, extracellular matrix, and blood vessels, in orchestrating the cancer‐specific metabolism and diversity of both mRNA and noncoding RNA, including micro RNA, long noncoding RNA, circular RNA among others. We also highlight the transcriptomic adaptations in response to the physicochemical idiosyncrasies of TME, which include tumor hypoxia, extracellular acidosis, and osmotic stress. Finally, we provide a nuanced analysis of existing and prospective therapeutics targeting TME to ameliorate cancer‐associated RNA metabolism, consequently thwarting the cancer progression. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing RNA Turnover and Surveillance > Regulation of RNA Stability RNA in Disease and Development > RNA in Disease Abstract : The heterogeneous population of malignant cells within a tumor, along with various non‐transformed cells, immune cells, soluble factors, extracellular matrix, extracellular vesicles, and tumor vasculature, constitute a complex ecosystem termed tumor microenvironment. The dynamic interaction within the tumor microenvironment orchestrates the neoplastic RNA metabolism and transcriptome diversity at various levels augmenting the malignant progression