Circ-IGF1R has pro-proliferative and anti-apoptotic effects in HCC by activating the PI3K/AKT pathway

Fu, Hangwei; Lin, Xia; Zhu, Yuanxin; Xiang, Lan; Kuang, Yi; Wang, Yuzhou; Ke, Zhigang; Yuan, Tao; Chen, Ping

doi:10.1016/j.gene.2019.144031

Cited by 54 publications

(41 citation statements)

References 38 publications

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“…Fu et al . found that circ‐IGF1R is upregulated in HCC tissues, cell proliferation was significantly attenuated by siRNA knockdown of circ‐IGF1R; circ‐IGF1R may, thus, play a carcinogenic role in HCC by activating the PI3K/AKT signaling pathway . In addition, Jiang et al .…”

Section: Discussionmentioning

confidence: 96%

“…18 Fu et al found that circ-IGF1R is upregulated in HCC tissues, cell proliferation was significantly attenuated by siRNA knockdown of circ-IGF1R; circ-IGF1R may, thus, play a carcinogenic role in HCC by activating the PI3K/AKT signaling pathway. 19 In addition, Jiang et al performed RNA-seq on the human bronchial epithelial cell line, BEAS-2B (BEAS-2B-T), transformed by benzo(a)pyrene (BaP), and found that circ-IGF1R is one of the circRNAs that play a potential role in the transformation of lung cancer cells. 20 However, the mechanism of action of circ-IGF1R and diagnosis and treatment using circ-IGF1R in lung cancer has not yet been clarified.…”

Section: Discussionmentioning

confidence: 99%

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Circ‐IGF1Rinhibits cell invasion and migration in non‐small cell lung cancer

Xiang

Chen

et al. 2020

Thoracic Cancer

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Background Circular RNA (circRNA) is a novel molecular marker and target candidate that is closely associated with tumor invasion and migration. The mechanism of action of hsa_circ_0005035 (circ‐IGF1R) in non‐small cell lung cancer remains unclear. In this study, we aimed to study the mechanism of action of circ‐IGF1R in lung cancer. Methods We screened circ‐IGF1R, one of the most notable differential expressions, from the Gene Expression Omnibus database, GSE104854, for further research. The expression level of circ‐IGF1R was examined using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) in five different lung cancer cell lines and 50 pairs of lung cancer and adjacent tissues. Wound‐healing and Transwell assays were used for verifying the biological function of circ‐IGF1R. The effect of overexpressing circ‐IGF1R on the transcriptome of whole lung cancer cells was explored in lung cancer cell lines using RNA‐seq. Results The expression level of circ‐IGF1R was notably lower in lung cancer tissues and lung cancer cell lines than in the adjacent normal tissues and cells (P < 0.0001). In addition, the expression level of circ‐IGF1R was associated with larger tumors (T2/T3/T4) and lymph node metastasis (N1/ N2/N3) (P < 0.05). The overexpression of circ‐IGF1R significantly inhibited the invasion and migration of the lung cancer cells. The potential network of circ‐IGF1R–miR‐1270–VANGL2 was preliminarily determined, and the expression patterns of miR‐1270 and VANGL2 were verified in lung cancer cell lines. Conclusion Circ‐IGF1R may inhibit lung cancer invasion and migration through a potential network of circ‐IGF1R–miR‐1270–VANGL2.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Circ‐IGF1Rinhibits cell invasion and migration in non‐small cell lung cancer

Xiang

Chen

et al. 2020

Thoracic Cancer

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“…For example, CircRNA PTPRM expression is significantly increased in HCC tissues compared with paired adjacent tissues, and its overexpression is correlated with HCC recurrence and metastasis in HCC patients . Another study exhibits that high level of circRNA IGF1R is correlated with tumor size in HCC patients . Regarding circ‐SMARCA5, as one of circRNAs, several publications reveal its participation in the tumorigenesis of various tumors, and circ‐SMARCA5 high expression is reported to be correlated with favorable clinicopathological features and prognosis in patients with cancers .…”

Section: Discussionmentioning

confidence: 97%

“…Until now, there are only preliminary investigations focusing on the role of circRNAs in cancers . Existing evidence demonstrates that circRNA expression is abnormal expressed in tumor tissues compared with adjacent tissues, and associated with clinical outcomes in patients with tumors . For example, CircRNA PTPRM expression is significantly increased in HCC tissues compared with paired adjacent tissues, and its overexpression is correlated with HCC recurrence and metastasis in HCC patients .…”

Section: Discussionmentioning

confidence: 99%

Circular RNA SMARCA5 correlates with favorable clinical tumor features and prognosis, and increases chemotherapy sensitivity in intrahepatic cholangiocarcinoma

Fang

2019

Clinical Laboratory Analysis

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Objective: This present study aimed to investigate the correlation of circular RNA SMARCA5 (circ-SMARCA5) with clinicopathological features and overall survival (OS), and the effect of circ-SMARCA5 on cell proliferation and chemotherapy sensitivity to cisplatin/gemcitabine in intrahepatic cholangiocarcinoma (ICC). Methods:Totally 92 primary ICC patients who underwent resection were recruited, and their tumor tissues and adjacent tissues were collected for circ-SMARCA5 detection. The effect of circ-SMARCA5 on cell proliferation and chemotherapy sensitivity was detected after circ-SMARCA5 overexpression plasmid transfection into TFK-1 and HuH-28 ICC cells.Results: Circ-SMARCA5 expression was reduced in ICC tumor tissues compared to adjacent tissues. Tumor circ-SMARCA5 high expression was negatively associated with Eastern Cooperative Oncology Group performance score, T stage, N stage, TNM stage, and abnormal CA199 status. Furthermore, OS was increased in patients with tumor circ-SMARCA5 high expression compared with those with low expression, and further multivariate Cox's regression demonstrated that tumor circ-SMARCA5 high expression was an independent predictive factor for longer OS. In TFK-1 and HuH-28 ICC cells, circ-SMARCA5 upregulation decreased cell proliferation, reduced relative cell viability in cisplatin-treated as well as gemcitabine-treated cells, and also decreased inhibitory concentration by 50% value (IC 50 ) of cisplatin and gemcitabine. Conclusion:The correlation of circ-SMARCA5 with favorable clinical tumor features, survival profile, and its promoting effect on chemotherapy sensitivity implies its potential as a valuable biomarker in monitoring disease progression and prognosis of ICC. K E Y W O R D Scell proliferation, chemotherapy sensitivity, circular RNA SMARCA5, intrahepatic cholangiocarcinoma, prognosis

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“…Besides, BRD4 was found to be a target of H19/miR-152-3p axis to promote the progression of MM [35]. Liu et al found that circ_8073 accelerated the proliferation of caprine endometrial epithelial cells through activating PI3K/AKT/mTOR pathway via miR-449a/CEP55 axis [36].…”

Section: Discussionmentioning

confidence: 99%

Circ_0007841 promotes the progression of multiple myeloma via miR-338-3p/BRD4 axis

Wang

Lin

Song

et al. 2020

Preprint

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Background The pathogenesis of multiple myeloma (MM) is not completely known. Herein, we explored the function and the working mechanism of circular RNA circ_0007841 in MM progression. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of circ_0007841, microRNA-338-3p (miR-338-3p) and bromodomain containing 4 (BRD4). The proliferation and metastasis of MM cells were examined by cell counting kit-8 (CCK8) assay and transwell assays. Flow cytometry was conducted to assess the cell cycle and the apoptosis of MM cells. The targets of circ_0007841 and miR-338-3p were predicted by circinteractome and targetscan softwares, and these predictions were confirmed by dual-luciferase reporter assay and RNA-pull down assay. The protein levels of BRD4, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K), PI3K, p-AKT serine/threonine kinase (p-AKT) and AKT were measured by Western blot assay. Exosomes were extracted using Exosome isolation kit. Results Circ_0007841 was highly expressed in bone marrow (BM)-derived plasma cells of MM patients and MM cells than that in healthy volunteers and normal plasma cells nPCs. Circ_0007841 promoted the proliferation, cell cycle and metastasis and impeded the apoptosis of MM cells. MiR-338-3p was a direct target of circ_0007841 in MM cells. Circ_0007841 accelerated the progression of MM through targeting miR-338-3p. BRD4 could directly bind to miR-338-3p in MM cells. MiR-338-3p exerted an anti-tumor role through targeting BRD4. Circ_0007841 promoted the activation of PI3K/AKT signaling via miR-338-3p/BRD4 axis. Exosomes generated from mesenchymal stromal cells (MSCs) elevated the malignant behaviors of MM cells via circ_0007841. Conclusion Circ_0007841 acted as an oncogene to promote the proliferation, cell cycle and motility and restrain the apoptosis of MM cells through sequestering miR-338-3p to up-regulate the expression of BRD4.

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Circ-IGF1R has pro-proliferative and anti-apoptotic effects in HCC by activating the PI3K/AKT pathway

Cited by 54 publications

References 38 publications

Circ‐IGF1Rinhibits cell invasion and migration in non‐small cell lung cancer

Circ‐IGF1Rinhibits cell invasion and migration in non‐small cell lung cancer

Circular RNA SMARCA5 correlates with favorable clinical tumor features and prognosis, and increases chemotherapy sensitivity in intrahepatic cholangiocarcinoma

Circ_0007841 promotes the progression of multiple myeloma via miR-338-3p/BRD4 axis

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