环状RNA:胃癌诊治的新星

Circular RNA:New Star in The Diagnosis and Treatment of Gastric Cancer

环状RNA(circular RNA,circRNA)是一类闭合环状结构的RNA分子,广泛分布于各种组织中,它比线性RNA更稳定。circRNA分为外显子circRNA、外显子-内含子circRNA和内含子circRNA等3类。circRNA的主要功能为充当微RNA海绵、与RNA结合蛋白结合、翻译成蛋白质和调节转录等。近年来,大量研究表明,circRNA的异常表达在胃癌发生发展过程中起着至关重要的作用。circPTPN22、hsa_circ_0001772、circCYFIP2、hsa_circ_0017639和circPIP5K1A等的上调以及hsa_circ_002059、hsa_circ_0000190和circMTO1等的下调与胃癌的增殖和转移密切相关;而hsa_circ_0001313等影响胃癌细胞的顺铂耐药性。组织、血浆及外泌体中circPTPN22、hsa_circ_102958、hsa_circ_0141633、hsa_circ_0065149和hsa_circ_0026344等是胃癌新型诊断标志物;而hsa_circ_0005529、circ-RanGAP1、circPIP5K1A和circMAT2B等有希望成为胃癌治疗的新靶点。这些胃癌相关circRNA的研究成果有助于认识胃癌发生机制,并为胃癌的诊治提供基础。

Circular RNAs(circRNAs)are RNA molecules with closed ring structure and are widely distributed in various tissues.circRNAs are more stable than linear RNAs.They can be divided into three categories:exonic circular RNA,exon-intron circular RNA,and circular intronic RNA.The main functions of circRNAs are acting as a sponge of microRNAs,binding to RNA binding proteins,affecting the formation of homologous linear mRNAs and regulating transcription.Besides,the latest research found that some circRNAs can directly code protein,which changed the impression that circRNAs only act as noncoding RNAs.This may provide a new idea for future studies of circRNAs.In recent years,a large number of studies have shown that the abnormal expression of circRNAs plays an important role in the occurrence and development of gastric cancer.The expression of circRNAs in tissues,plasma and exosomes is variable between healthy individuals and patients with gastric cancer.Some gastric cancer-associated circRNAs are more sensitive and more specific than traditional gastric cancer markers.For example,hsa_circ_0065149 level is significantly decreased in exosome of gastric cancer patient,while the levels of circPTPN22,hsa_circ_0004771,and hsa_circ_0141633 in the plasma of gastric cancer patients are increased,indicating the potential of circRNAs as novel diagnostic markers for gastric cancer.Studies on gastric cancer-associated drug resistance have found that some circRNAs including circ-PVT1,circCUL2,hsa_circ_0001313,hsa_circ_0110805,and circVAPA affect the chemoresistance of gastric cancer cells through the circRNA/miRNA/mRNA arises.The main functions of circRNAs are by acting as microRNA sponge to regulate the expression of targeted m RNAs,functioning as tumor promoter or suppressor,thereby affecting gastric cancer proliferation,differentiation and metastasis.The aberrant expression of circRNAs plays a crucial role in gastric carcinogenesis.For example,circRBM33,one of the gastric cancer-associated upregulated circRNAs,upregulates the expression of interleukin-6(IL-6)through miR-149/IL-6 axis,which in turn promotes gastric cancer proliferation.Hsa_circ_002059 inhibits gastric cancer proliferation and migration by inhibiting the expression of miR-182 and inducing the expression of Metastasis suppressor 1(MTSS1).In addition,hsa_circ_0005529,circRanGAP1,circPIP5K1A,circMAT2B,and circMTO1 may be promising as novel targets for the treatment of gastric cancer.The results of studies on gastric cancer-related circRNAs are helpful for us to understand the mechanism underlying gastric cancer occurrence and provide basics for the diagnosis and treatment of gastric cancer.