Expression alteration and function small noncoding RNAs in gastric cancer

Background Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the fifth most common cause of cancer-related death with a heterogeneous and aggressive behavior. GC is a multifactorial disease characterized by complex interactions between genetic, epigenetic, and environmental factors, leading to aberrant cellular behaviors, including uncontrolled proliferation, evasion of apoptosis, and metastasis. The dysregulation of non-coding RNAs (ncRNAs) has been implicated in these processes, highlighting their potential as both biomarkers and therapeutic targets in GC. NcRNAs, particularly small non-coding RNAs such as microRNAs (miRNAs), play a critical role in the pathogenesis of GC through their ability to regulate gene expression and influence various cellular processes. NcRNAs are broadly divided into two groups based on their length, including long ncRNAs (lncRNAs; longer than ۲۰۰ nucleotides) and small ncRNAs (shorter than ۲۰۰ nucleotides). Small ncRNAs are further classified into microRNAs (miRNAs), small interfering RNAs (siRNAs), piwi-interacting RNAs (piRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs). MicroRNAs, typically ۱۸-۳۰ nucleotides in length, function primarily by binding to complementary sequences on target mRNAs, leading to mRNA degradation or inhibition of translation. This post-transcriptional regulation is crucial in maintaining cellular homeostasis, and alterations in miRNA expression can disrupt this balance, contributing to tumorigenesis. MiRNAs are implicated in the progression of human GC, such as miR-۵۶۷, miR-۳۴a, miR-۲۱, miR-۷۱۸, miR-۳۲۴-۳p, and miR-۶۷۵-۳p. Studies have shown that specific miRNAs such as miR-۲۲ and miR-۶۷۵ are upregulated in GC tissues, promoting cell proliferation and migration by targeting tumor suppressor genes like RUNX۱ and TOB۱. Conversely, other miRNAs may be downregulated, leading to the loss of their tumor-suppressive functions. The downregulation of piRNA-۸۲۳ has been associated with inhibited cell growth in GC, although the specific mechanisms remain to be fully elucidated. Moreover, aberrant expression of miRNA can is involved in differentiation, apoptosis, and survival through signaling pathways, such as PI۳K/AKT/mTOR, MAPK, and Wnt/β-catenin. Translational research suggests that piRNAs (~۲۱–۳۵ nucleotides in length) may regulate key genes and pathways associated with GC progression, although the specific mechanisms are not fully elucidated. The typical function of piRNAs is to silence transposons by guiding PIWI proteins to cleave target transposon mRNAs or binding to the promoters of transposons to silence their transcriptions. The piRNAs expression profiling between GC tissues and adjacent non-cancerous tissues revealed a total of ۸۷۵۹ piRNAs. The piR-۸۲۳ was significantly downregulated in GC tissues, revealing that piR-۸۲۳ analogues effectively inhibited GC cell proliferation. In contrast, piR-۶۵۱ was significantly upregulated in GC, and transfection with piR-۶۵۱ inhibitors blocked GC cell growth and induced G۲/M phase arrest. To explore the potential clinical utility of piRNAs, the results indicate that piRNAs such as piR-۶۵۱ and piR-۸۲۳ may be more sensitive biomarkers than serum CEA and CA۱۹-۹ for GC diagnosis. Conclusion: The altered expression of small non-coding RNAs, particularly miRNAs, plays a pivotal role in the development and progression of GC. Their ability to regulate key signaling pathways and cellular processes underscores their potential utility as biomarkers for early detection and prognosis, as well as targets for therapeutic strategies.

کلیدواژه ها:

Gastric cancer ، microRNAs ، piRNAs