LncRNA NKX2‐1‐AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR‐2 signaling pathway in gastric cancer

Teng, Fei; Zhang, Ju‐Xiang; Chen, Yi; Shen, Xiaodong; Su, Chang; Guo, Yanjiao; Wang, Pu‐Hua; Shi, Chencheng; Lei, Ming; Cao, Yiou; Liu, Shao‐Qun

doi:10.1002/1878-0261.12911

Cited by 66 publications

(40 citation statements)

References 41 publications

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“…Third, considering that TARBP2 involves in multiple cellular processes, particularly its function in regulating the accuracy of miRNA processing ( 46 ), we aimed to elucidate an epigenetic pathway via miRNAs for the TARBP2-SERPINE1 axis in HCC progression. Our findings suggested that sh- TARBP2 reduced the synthesis of mature miR-145, which have been identified to directly target SERPINE1 in previous reports ( 17 , 47 , 48 ). Next, we validated the relationship between SERPINE1 and miR-145 in HCC using dual luciferase assays and clinical samples.…”

Section: Discussionsupporting

confidence: 78%

Loss of TARBP2 Drives the Progression of Hepatocellular Carcinoma via miR-145-SERPINE1 Axis

Chen

Ran

et al. 2021

Front. Oncol.

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The clinical outcomes of hepatocellular carcinoma (HCC) remain dismal. Elucidating the molecular mechanisms for the progression of aggressive HCC holds the promise for developing novel intervention strategies. The transactivation response element RNA-binding protein (TRBP/TARBP2), a key component of microRNA (miRNA) processing and maturation machinery has been shown to play conflicting roles in tumor development and progression. We sought to investigate the expression of TARBP2 in HCC using well-characterized HCC cell lines, patient-derived tissues and blood samples. Additionally, the potential prognostic and diagnostic value of TARBP2 in HCC were analyzed using Kaplan-Meier plots and ROC curve. Cell counting kit‐8 (CCK‐8), wound healing and transwell assays examined the ability of TARBP2 to induce cell proliferation, migration, and invasion in HCC cell lines. RNA sequencing was applied to identify the downstream elements of TARBP2. The interaction of potential targets of TARBP2, miR‐145 and serpin family E member 1 (SERPINE1), was assessed using luciferase reporter assay. TARBP2 expression was down-regulated in HCC cell lines relative to normal hepatocyte cells, with a similar pattern further confirmed in tissue and blood samples. Notably, the loss of TARBP2 was demonstrated to promote proliferation, migration, and invasion in HCC cell lines. Interestingly, the reduction of TARBP2 was shown to result in the upregulation of SERPINE1, also known as plasminogen activator inhibitor (PAI-1), which is a vital gene of the HIF-1 signaling pathway. Knockdown of SERPINE1 rescued the TARBP2-lost phenotype. Moreover, TARBP2 depletion induced the upregulation of SERPINE1 through reducing the processing of miR-145, which directly targets SERPINE1. Finally, overexpression of miR-145 repressed SERPINE1 and rescued the functions in sh-TARBP2 HCC cells. Our findings underscore a linear TARBP2-miR-145-SERPINE1 pathway that drives HCC progression, with the potential as a novel intervention target for aggressive HCC.

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Section: Discussionsupporting

confidence: 78%

Loss of TARBP2 Drives the Progression of Hepatocellular Carcinoma via miR-145-SERPINE1 Axis

Chen

Ran

et al. 2021

Front. Oncol.

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“…Excessive angiogenesis is an essential characteristic of cancer, which account for the tumor proliferation ( Liu et al, 2019 ), invasion ( Zeng et al, 2018 ), chemoresistance ( Marti et al, 2015 ), etc., Emerging evidences have indicated that lncRNAs participate in regulating malignant phenotypes and act as critical clinical biomarkers for diagnosis and prognosis in multiple malignancies ( Yang et al, 2019 ; Zhao et al, 2019 ; Gao et al, 2020 ; Shi et al, 2021 ). Although several angiogenesis-related lncRNAs have been identified in gastric cancers ( Liu H. T. et al, 2020 ; Teng et al, 2021 ), effective anti-angiogenesis strategies in GC are still limited and the underlying mechanisms remain to be further disclosed.…”

Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated Angiogenesis

Qiu

et al. 2021

Front. Cell Dev. Biol.

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BackgroundLong non-coding RNAs (lncRNAs) have been indicated to play critical roles in gastric cancer (GC) tumorigenesis and progression. However, their roles in GC remain to be further elucidated.MethodsRT-qPCR and fluorescence in situ hybridzation (FISH) were conducted to detect the expression of lncRNA NEAT1 in GC tissues and cell lines. Gene Set Enrichment Analysis (GSEA) was performed to screen out potential phenotypes and pathways that NEAT1 may participate in. NEAT1-silenced AGS and MGC803 cells were constructed and a series of functional experiments to investigate the roles of NEAT1 in GC angiogenesis both in vitro and in vivo. RNA pull down and luciferase reporter assays were utilized to illustrate the mechanisms underlying the functions of NEAT1 in GC.ResultsWe observed that NEAT1 was upregulated in most GC specimens and cell lines. NEAT1 high was correlated with poor prognosis of GC patients. In vitro experiments showed that NEAT1 promoted GC angiogenesis by enhancing proliferation, migration, and tube formation ability of endothelial cells. Mechanism researches revealed that NEAT1 could competitively sponge miR-17-5p which targeted TGFβR2 directly. Subsequently, activate TGFβ/Smad pathway by following with upregulation of a series of classical proangiogenic factors especially VEGF.ConclusionThe study unveiled that the LncRNA NEAT1/miR-17-5p/TGFβR2 axis is a novel mechanism in GC angiogenesis. Disrupting this axis may be a potential strategy for GC treatment.

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“…The detection of protein expression was conducted referring to the descriptions of issued studies [ 18 , 19 ]. The primary antibodies against collagen I (ab34710, 1:1000), collagen IV (ab7536, 1:1000), HMGA2 (ab207301, 1:1000) and GAPDH (ab181602, 1:3000) were acquired from Abcam (Cambridge, UK).…”

Section: Methodsmentioning

confidence: 99%

Circ-ACTR2 aggravates the high glucose-induced cell dysfunction of human renal mesangial cells through mediating the miR-205-5p/HMGA2 axis in diabetic nephropathy

Yun

Ren

Liu

et al. 2021

Diabetol Metab Syndr

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Background Circular RNAs (circRNAs) have been considered as pivotal biomarkers in Diabetic nephropathy (DN). CircRNA ARP2 actin-related protein 2 homolog (circ-ACTR2) could promote the HG-induced cell injury in DN. However, how circ-ACTR2 acts in DN is still unclear. This study aimed to explore the molecular mechanism of circ-ACTR2 in DN progression, intending to provide support for the diagnostic and therapeutic potentials of circ-ACTR2 in DN. Methods RNA expression analysis was conducted by the quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cell growth was measured via Cell Counting Kit-8 and EdU assays. Inflammatory response was assessed by Enzyme-linked immunosorbent assay. The protein detection was performed via western blot. Oxidative stress was evaluated by the commercial kits. The molecular interaction was affirmed through dual-luciferase reporter and RNA immunoprecipitation assays. Results Circ-ACTR2 level was upregulated in DN samples and high glucose (HG)-treated human renal mesangial cells (HRMCs). Silencing the circ-ACTR2 expression partly abolished the HG-induced cell proliferation, inflammation and extracellular matrix accumulation and oxidative stress in HRMCs. Circ-ACTR2 was confirmed as a sponge for miR-205-5p. Circ-ACTR2 regulated the effects of HG on HRMCs by targeting miR-205-5p. MiR-205-5p directly targeted high-mobility group AT-hook 2 (HMGA2), and HMGA2 downregulation also protected against cell injury in HG-treated HRMCs. HG-mediated cell dysfunction was repressed by miR-205-5p/HMGA2 axis. Moreover, circ-ACTR2 increased the expression of HMGA2 through the sponge effect on miR-205-5p in HG-treated HRMCs. Conclusion All data have manifested that circ-ACTR2 contributed to the HG-induced DN progression in HRMCs by the mediation of miR-205-5p/HMGA2 axis.

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LncRNA NKX2‐1‐AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR‐2 signaling pathway in gastric cancer

Cited by 66 publications

References 41 publications

Loss of TARBP2 Drives the Progression of Hepatocellular Carcinoma via miR-145-SERPINE1 Axis

Loss of TARBP2 Drives the Progression of Hepatocellular Carcinoma via miR-145-SERPINE1 Axis

LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated Angiogenesis

Circ-ACTR2 aggravates the high glucose-induced cell dysfunction of human renal mesangial cells through mediating the miR-205-5p/HMGA2 axis in diabetic nephropathy

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