CircRNA-100338 Is Associated With mTOR Signaling Pathway and Poor Prognosis in Hepatocellular Carcinoma

Huang, Xiuyan; Huang, Zili; Zhang, Ping-Bao; Huang, Xinyu; Huang, Jin; Wang, Hongcheng; Xu, Bin; Zhou, Jian; Tang, Zhao‐You

doi:10.3389/fonc.2019.00392

Cited by 65 publications

(71 citation statements)

References 40 publications

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“…circRNAs were identified to be important regulators in human cancers. In HCC, we, together with other research teams [5][6][7], have identified that a series of cir-cRNAs were dysregulated in cancer samples and associated with tumor progression, which may serve as promising biomarkers for cancer. CircRNAs are involved in regulating multiple cancer-related biological processes and pathways, including cell growth [8], metastasis [9], and apoptosis [10].…”

Section: Introductionmentioning

confidence: 90%

“…The HCC cell lines were cultured following procedures stated in our previous reports [5,12]. Briefly, the noninvasive human liver cell line of L02 (normal), human HCC cell lines of Hep3B with low invasiveness, and highly invasive HLE, Huh7, BEL7402, SMCC7721, MHCC97L, MHCC97H, HCCLM3 and HCCLM6 were prepared in this study, which were widely used in previous studies [17,18].…”

Section: Hcc Cell Line and Cell Culturementioning

confidence: 99%

“…Circ-CDYL interacts with HDGF and HIF1AN to regulate HCC stemness and growth [6]. We previously identified a series of dysregulated circRNAs in HCC and focused on examining the roles of circRNA-100,338 in HCC [5,12]. We have demonstrated that circRNA-100,338 is overexpressed and associated with mTOR signaling pathway [5] and poor prognosis [12] in HCC.…”

Section: Introductionmentioning

confidence: 99%

“…We previously identified a series of dysregulated circRNAs in HCC and focused on examining the roles of circRNA-100,338 in HCC [5,12]. We have demonstrated that circRNA-100,338 is overexpressed and associated with mTOR signaling pathway [5] and poor prognosis [12] in HCC. Of note, circRNAs can be detected in blood and urine samples of patients, suggesting that circRNAs may be a type of non-invasive markers for human cancer diagnosis [4].…”

Section: Introductionmentioning

confidence: 99%

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Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis

Huang

et al. 2020

J Exp Clin Cancer Res

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Background: Exosomes play crucial roles in regulating the crosstalk between normal and cancer cells in the tumor microenvironment, and in regulating cancer proliferation, migration and invasion through their cargo molecules. Methods: We analyzed the pro-invasiveness of exosomal circRNA-100,338 in HCC using the transwell invasion assay. The co-culture of human umbilical vein endothelial cells (HUVEC) and exosomes derived from HCC cell lines were used to evaluate the impact of HCC derived exosomes on HUVEC. Nude mice models were used to validate the findings in vitro. Clinically, quantitative RT-PCR was used to quantify the expression of serum exosomal circRNA-100,338 in HCC patients at both pre-surgery within one week and post-surgery within three weeks. Results: We aim to investigate the pro-invasive role of exosomal circRNA-100,338 in HCC metastasis. We for the first time demonstrated that circRNA-100,338 was highly expressed in both highly metastatic HCC cells and their secreted exosomes. The transwell invasion assay showed that the overexpression or knockdown of exosomal circRNA-100,338 significantly enhanced or reduced the invasive abilities of HCC cells. Subsequently, in vitro and in vivo assays showed that exosomal circRNA-100,338 affected the cell proliferation, angiogenesis, permeability, and vasculogenic mimicry (VM) formation ability of human umbilical vein endothelial cells (HUVEC), and tumor metastasis. Furthermore, we also observed that the persistent high expression of exosomal circRNA-100,338 in serum of HCC patients who underwent curative hepatectomy may be a risk indicator of pulmonary metastasis and poor survival. Conclusions: Our findings indicated that metastatic ability of HCC cells could be enhanced by transferring exosomal circRNA-100,338 to recipient HUVECs, which could affect proangiogenic activity by regulating angiogenesis.

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Section: Introductionmentioning

confidence: 90%

Section: Hcc Cell Line and Cell Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis

Huang

et al. 2020

J Exp Clin Cancer Res

Self Cite

291

198

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show abstract

“…recent studies have indicated that circrnas may serve important roles in driving cancer initiation and progression, and have the potential to serve as biomarkers for predicting cancer progression (7,8). accumulating evidence has demonstrated that circrnas regulate Hcc progression and serve as potential biomarkers for predicting cancer prognosis (9)(10)(11)(12)(13)(14)(15). However, a considerable number of circrnas remain to be elucidated in Hcc.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA Circ100084 functions as sponge of miR‑23a‑5p to regulate IGF2 expression in hepatocellular carcinoma

Yang

et al. 2020

Mol Med Report

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Hepatocellular carcinoma (Hcc) has become a major cause of cancer-related mortality worldwide. circular rnas (circrnas) are non-coding rnas that serve important roles in multiple cancers. However, the role of circrnas in Hcc remains largely unknown. in the present study, a circrna microarray dataset of Hcc samples, GSe97332, was downloaded from the gene expression omnibus database. Following data preprocessing, differentially expressed circrnas between Hcc tissues and normal tissues were determined using Geo2r. The circrna-mirna interactions were predicted by the miranda database. The mirTarbase database was used to search for target genes of the mirnas. a circrna-mirna-mrna network was constructed using cytoscape based on the obtained circrna, mirna and mrna. in this network, the upregulated circrna hsa_circrna_100084 was found to be involved in a competing endogenous relationship of hsa_ circrna_100084-hsa-mir-23a-5p-insulin-like growth factor 2 (IGF2). The differential expression of hsa_circrna_100084, hsa-mir-23a-5p and IGF2 in Hcc tissues and liver cancer cells was validated by reverse transcription-quantitative Pcr. additionally, the interactions between hsa-mir-23a-5p with hsa_circrna_100084 and IGF2 were validated by dual-luciferase reporter assays. Knocking down hsa_circrna_100084 inhibited the proliferation, migration and invasion of liver cancer cells, while the simultaneous overexpression of IGF2 reversed the effects of hsa_circrna_100084 knockdown. The results show that hsa_circrna_100084 could promote the expression of IGF2 by acting as a sponge of hsa-mir-23a-5p in liver cancer cells.

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

Cao

Wang

et al. 2022

Clinical Laboratory Analysis

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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).

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CircRNA-100338 Is Associated With mTOR Signaling Pathway and Poor Prognosis in Hepatocellular Carcinoma

Cited by 65 publications

References 40 publications

Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis

Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis

Circular RNA Circ100084 functions as sponge of miR‑23a‑5p to regulate IGF2 expression in hepatocellular carcinoma

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

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