Molecular regulation of hypoxia through the lenses of noncoding RNAs and epitranscriptome

Abstract

Cells maintain homeostasis in response to environmental stress through specific cell stress responses. Hypoxic stress, well known to be associated with diverse solid tumors, is one of the main reasons for cancer-related mortality. Although cells can balance themselves well during hypoxic stress, the underlying molecular mechanisms are not well understood. The enhanced appreciation of diverse roles played by noncoding transcriptome and epigenome in recent years has brought to light the involvement of noncoding RNAs and epigenetic modifiers in hypoxic regulation. The emergence of techniques like deep sequencing has facilitated the identification of large numbers of long noncoding RNAs (lncRNAs) that are differentially regulated in various cancers. Similarly, proteomic studies have identified diverse epigenetic modifiers such as HATs, HDACs, DNMTs, polycomb groups of proteins, and their possible roles in the regulation of hypoxia. The crosstalk between lncRNAs and epigenetic modifiers play a pivotal role in hypoxia-induced cancer initiation and progression. Besides the lncRNAs, several other noncoding RNAs like circular RNAs, miRNAs, and so forth are also expressed during hypoxic conditions.Hypoxia has a profound effect on the expression of noncoding RNAs and epigenetic modifiers. Conversely, noncoding RNAs/epigenetic modifies can regulate the hypoxia signaling axis by modulating the stability of the hypoxiainducible factors (HIFs). The focus of this review is to illustrate the molecular orchestration underlying hypoxia biology, especially in cancers, which can help in identifying promising therapeutic targets in hypoxia-induced cancers.

Roles of circRNA dysregulation in esophageal squamous cell carcinoma tumor microenvironment

“…Thus, several adaptive cellular responses and biological changes are initiated when cancer cells sense a drop in oxygen levels, causing them to swiftly adapt to the hypoxic environment and accelerate cancer progression ( 182 ). Recent studies have revealed that circRNAs play crucial roles in developing hypoxic microenvironments and exhibit variable expression in response to hypoxia ( 183 , 184 ). According to previous studies, miR-497-5p is targeted by PRKAA1 and contributes to ESCC cell proliferation and motility control by being minimally expressed in ESCC ( 185 ).…”

Identification of region-specific splicing QTLs in human hippocampal tissue and its distinctive role in brain disorders

“… 1 , 2 By alternative pre-mRNA splicing, multiple transcripts, and protein isoforms can be generated from a single gene with different biological functions. 3 Emerging as one of the most important mechanisms regulating gene expression, AS events affects about 95% of human multi-exon genes, 4 which often occur in a cell or tissue-type specific manner. 5 Notably, the molecular mechanism of AS is particularly prevalent and intricate in the human brain, 6 suggesting that such highly complex AS regulation in brain tissue can play a crucial role in the normal development and functional maintenance of the central nervous system.…”

Identification of long non-coding RNAs as substrates for cytoplasmic capping enzyme

“…Further, lncRNAs such as MALAT1 act as scaffolds by providing surfaces to form ribonucleoprotein complexes [39]. Thus, depending on the biological cues, lncRNAs can function as positive or negative regulators of gene expression [40][41][42][43]. LncRNAs can also act as architectural RNA, or arcRNA [44].…”