Comprehensive circular RNA profiling identifies CircFAM120A as a new biomarker of hypoxic lung adenocarcinoma

Cheng, Xinghua; Qiu, Jin; Wang, Sainan; Yang, Yunhai; Guo, Mingwei; Wang, Dongmei; Luo, Qingquan; Xu, Lingyan

doi:10.21037/atm.2019.08.79

Cited by 28 publications

(24 citation statements)

References 37 publications

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“…We observed that circ_0008193 was significantly downregulated in LUAD tumor tissues and cell lines, as well as in hypoxia-treated A549 and H1975 cells (with HIF1A upregulation). These data agreed with a previous study [ 29 ]. In this study, we further examined the biologic role of circ_0008193 in LUAD cells.…”

Section: Discussionsupporting

confidence: 94%

“…Dozens of circRNAs have also been declared to be significantly abundantly altered upon hypoxia in cervical, breast, and lung cancer cells in vitro [ 28 ]. Moreover, the circRNA expression profile was comprehensively compared in A549 cells under normoxia and hypoxia [ 29 ]. Since hypoxia is crucial to the initiation and progression of tumor metastasis, several circRNAs have been demonstrated to participate in LUAD cell migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

“…The growth of neoplasms mediated by A549 cells was restrained by circ_0008193 overexpression in vivo . With inspiration from the prediction of target miRNAs by Cheng et al [ 29 ], we chose miR-1180-3p for further confirmation. Here, we observed that HIF1A upregulation in hypoxia-treated A549 and H1975 cells led to circ_0008193 inhibition (as well as miR-1180-3p promotion), and overexpressing circ_0008193 caused HIF1A downregulation (accompanied by miR-1180-3p deficiency).…”

Section: Discussionmentioning

confidence: 99%

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A Regulatory Axis of circ_0008193/miR-1180-3p/TRIM62 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Lung Adenocarcinoma Cells Under Hypoxia

et al. 2020

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Background Expression profiles of circular ribonucleic acids (circRNAs) have been recently reported in lung cancers including lung adenocarcinoma (LUAD). Hypoxia is a hallmark of lung cancers. However, the role of hsa_circ_0008193 (circ_0008193) in LUAD under hypoxia remains to be illuminated. Material/Methods Gene expression levels were detected using real-time quantitative polymerase chain reaction and western blotting. Cell proliferation, migration, invasion, and Warburg effect were detected using 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide assay, transwell assays, special kits, and xenograft experiments. The relationship among circ_0008193, micro (mi)RNA (miR)-1180-3p, and tripartite motif containing 62 (TRIM62) was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation. Results Expression of circ_0008193 was downregulated in human LUAD tumor tissues and cell lines (A549 and H1975), accompanied by miR-1180-3p upregulation and TRIM62 downregulation. Moreover, circ_0008193 downregulation was correlated with tumor size and lymph node metastasis. Functionally, circ_0008193 overexpression inhibited cell viability, glucose uptake, lactate production, migration, and invasion, as well as expression of hexokinase II, lactate dehydrogenase A, matrix metalloproteinase 2 (MMP2), and MMP9 in hypoxic LUAD cells in vitro . Furthermore, tumor growth of A549 cells in vivo was also hindered by circ_0008193 overexpression. Mechanically, circ_0008193 regulated TRIM62 expression via sponging miR-1180-3p, and TRIM62 was targeted by miR-1180-3p. Both miR-1180-3p upregulation and TRIM62 downregulation could abolish the suppressive role of circ_0008193 in LUAD cells. Conclusions Upregulating circ_0008193 inhibited LUAD cell proliferation, migration, invasion, and Warburg effect under hypoxia in vitro and in vivo through regulation of the miR-1180-3p/TRIM62 axis.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A Regulatory Axis of circ_0008193/miR-1180-3p/TRIM62 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Lung Adenocarcinoma Cells Under Hypoxia

et al. 2020

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“…As a novel hotspot of the ncRNA field, hypoxia-responsive circRNAs (HRCs) have been shown to be of great importance. However, unlike miRNAs and lncRNAs, the mechanisms of HIF-1α-mediated HRC expression are not fully understood [28]. Similarly, several studies uncovered that HIF-1α can directly regulate cir-cRNAs at the transcriptional level through HREs, but more mechanisms have not been reported [29].…”

Section: Regulation Of Ncrnas By Hif-1αmentioning

confidence: 99%

“…In addition, the expression of circFAM120A was significantly downregulated in both hypoxic lung adenocarcinoma cells and cancer tissue from patients with lymph node metastasis, implying its potential to be a new biomarker of lung adenocarcinoma hypoxia [28]. Moreover, circRNAs lack a 5' cap and 3' ends, endowing them with more stable properties than parent linear RNAs [191].…”

Section: Perspectives On Hif-1α and Ncrnas In Clinical Practicementioning

confidence: 99%

The interplay between HIF-1α and noncoding RNAs in cancer

Peng

Han

et al. 2020

J Exp Clin Cancer Res

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Hypoxia is a classic characteristic of the tumor microenvironment with a significant impact on cancer progression and therapeutic response. Hypoxia-inducible factor-1 alpha (HIF-1α), the most important transcriptional regulator in the response to hypoxia, has been demonstrated to significantly modulate hypoxic gene expression and signaling transduction networks. In past few decades, growing numbers of studies have revealed the importance of noncoding RNAs (ncRNAs) in hypoxic tumor regions. These hypoxia-responsive ncRNAs (HRNs) play pivotal roles in regulating hypoxic gene expression at the transcriptional, posttranscriptional, translational and posttranslational levels. In addition, as a significant gene expression regulator, ncRNAs exhibit promising roles in regulating HIF-1α expression at multiple levels. In this review, we briefly elucidate the reciprocal regulation between HIF-1α and ncRNAs, as well as their effect on cancer cell behaviors. We also try to summarize the complex feedback loop existing between these two components. Moreover, we evaluated the biomarker potential of HRNs for the diagnosis and prognosis of cancer, as well as the potential clinical utility of shared regulatory mechanisms between HIF-1α and ncRNAs in cancer treatment, providing novel insights into tumorigenicity, which may lead to innovative clinical applications.

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