Abstract
Circular RNAs (circRNAs), as a recently established group of endogenous noncoding RNAs, have been involved in the occurrence and development of different malignancies. Gastric cancer (GC) remains a globally significant contributor to death in cancer patients due to insufficient early diagnosis, limited treatment measures, and poor prognosis. An increasing number of studies have found that many circRNAs are dysregulated in GC and are closely associated with its tumorigenesis and metastasis. Thus, circRNAs have the potential to serve as diagnostic and prognostic biomarkers and even therapeutic targets. This review comprehensively summarizes the most recent findings on how circRNAs influence GC progression and their clinical value. In addition, we present several methological deficiencies in the studies and provide some promising ideas for future research.
Highlights
In the 21st century, cancer has become one of the leading global health problems with increasing awareness among medical institutions and the general public
The occurrence of intron pairing-driven circularization is based on intronic complementary pairing of flanking intron sequences such as Alu elements and RNA-binding proteins (RBPs), which can facilitate the formation of ecircRNAs in the mammalian pre-mRNA splicing system after removal of discontinuous intron sequences [16,17,18,19]
There is accumulating evidence that this new type of RNAs is characterized by various expression patterns, complicated regulatory networks, and emerging roles at multiple molecular levels including miRNA, mRNA, and protein
Summary
In the 21st century, cancer has become one of the leading global health problems with increasing awareness among medical institutions and the general public. The activities of these trans-acting factors influence the levels of circRNAs and their related linear mRNAs. The occurrence of intron pairing-driven circularization is based on intronic complementary pairing of flanking intron sequences such as Alu elements and RNA-binding proteins (RBPs), which can facilitate the formation of ecircRNAs in the mammalian pre-mRNA splicing system after removal of discontinuous intron sequences [16,17,18,19]. Several critical sequences contribute to intron circularization including the 7 nucleotide (nt) GU-rich element near the 5′ splice site, the 11 nt C-rich element close to the 3′ branchpoint, and the RNA lariat debranching enzyme Dbr element [21, 22] Among these three elements, the 5′ ss-GU exhibits the best promotion effect for intron circularization; Dbr might play an indirect role or work together with other factors in this process [22]. Human cells have all of the necessary machinery to produce tricRNAs [27], which have been identified in many human cells such as HeLa cervical cancer and human embryonic kidney 293T cells [26]
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