The roles and mechanisms of circular RNAs related to mTOR in cancers

Abstract

Background Circular RNAs (circRNAs) are stable molecules with covalently closed structures that have an irreplaceable role in the occurrence, progression, and even treatment of plenty of cancers. Mammalian/mechanistic target of rapamycin (mTOR) is a key regulator in cancers and plays several biological functions, such as proliferation, migration, invasion, autophagy, and apoptosis. Methods All data were collected through PubMed and CNKI, using terms including “circRNA,” “mTOR,” “caner,” “signaling pathway,” “biomarker,” “diagnosis,” “treatment.” Articles published in Chinese and English were included. Results In this review, the expression, function, and mechanism of circRNA‐associated mTOR in cancers were described. CircRNA‐associated‐mTOR can regulate the progression and therapy of a variety of cancers in multiple signaling pathways, such as phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (Akt)/mTOR, mitogen‐activated protein kinase (MAPK)/mTOR, and AMP‐activated protein kinase (AMPK)/mTOR axis. These cancers including esophageal carcinoma (circLPAR3, ciRS‐7), gastric cancer (circNRIP1, hsa_circ_0010882, hsa_circ_0000117, hsa_circ_0072309, and circST3GAL6), colorectal cancer (hsa_circ_0000392, hsa_circ_0084927, hsa_circ_0104631, and circFBXW7), liver cancer (circC16orf62, hsa_circ_100338, hsa_circ_0004001, hsa_circ_0004123, hsa_circ_0075792, hsa_circ_0079299, and hsa_circ_0002130), pancreatic cancer (circ‐IARS and circRHOBTB3), renal carcinoma (ciRS‐7), bladder cancer (circUBE2K), prostate cancer (circMBOAT2 and circ‐ITCH), ovarian cancer (circEEF2, circRAB11FIP1, circMYLK, and circTPCN), endometrial cancer (hsa_circ_0002577 and circWHSC1), lung cancer (circHIPK3, hsa_circ_0001666), thyroid cancer (hsa_circ_0007694 and hsa_circ_0008274), glioma (circGFRA1, circ‐MAPK4, circPCMTD1, and hsa_circ_0037251), osteosarcoma (circTCF25), leukemia (circ‐PRKDC), and breast cancer (hsa_circ_0000199, circUBAP2, and circWHSC1).

Hsa_circ_0010882 facilitates hepatocellular carcinoma progression by modulating M1/M2 macrophage polarization

“…In addition, circ_0010882 facilitates the biological activities of gastric cancer cells by activation of the PI3K/Akt/mTOR pathway. 17,31 The specific mechanism of circ_0010882 in HCC is required.…”

“…Current data suggest that circ_0010882 may regulate macrophage polarization in HCC by targeting miR‐382. In addition, circ_0010882 facilitates the biological activities of gastric cancer cells by activation of the PI3K/Akt/mTOR pathway 17,31 . The specific mechanism of circ_0010882 in HCC is required.…”

Circular RNAs in the chemoresistance of triple‐negative breast cancer: A systematic review

“…In recent years, increasing attention has been given to the regulatory role of circRNAs in signalling pathways. A previous study found that two circRNAs (hsa_circ_0000199 and circUBAP2) promote cisplatin resistance by activating the PI3K/Akt/mTOR pathway (Cao et al, 2022). In this study, we found that in addition to the two kinds of circRNAs, circABCB1, circEPHA3.1 and circEPHA3.2, and circWAC could also regulate the PI3K/Akt signalling pathway.…”

The potential of circHIPK3 as a biomarker in chronic myeloid leukemia

“…The inhibition of miRNAs, also known as the sponge mechanism, occurs with the retention of miRNAs in the complementary binding sites of circRNAs, preventing their action on the target messenger RNA (mRNA) ( 24 ). Transcriptional regulation occurs through the interaction of circRNAs with promoter regions by binding to U1 snRNP (small nuclear ribonucleoprotein U1) and Pol II (RNA polymerase II), which are important factors involved in mRNA processing ( 25 ). CirRNAs can also interfere with the interaction between different proteins by bringing their interaction sites closer or further apart, act in protein recruitment, and even have their own sequence translated ( 7 ).…”