Circular RNA HIPK3 induces cell proliferation and inhibits apoptosis in non-small cell lung cancer through sponging miR-149

Lü, Hao; Han, Xinwei; Ren, Jianzhuang; Ren, Kewei; Li, Zong-Ming; Sun, Zhanguo

doi:10.1080/15384047.2019.1669995

Cited by 58 publications

(34 citation statements)

References 19 publications

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“…Non-invasive prognostic biomarkers are needed for the diagnosis of the advanced NSCLC patients with different histological types [18]. With the advance in the study of the molecular basis about lung cancer progression, targeted therapies have been used for NSCLC treatment [19]. CircRNAs are a group of non-coding RNAs with a stable closed-loop structure which prevents them from decomposing by the enzymes [20].…”

Section: Discussionmentioning

confidence: 99%

Circular RNA hsa_circ_0072309 inhibits non-small cell lung cancer progression by sponging miR-580-3p

et al. 2020

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Objective: Non-small cell lung cancer (NSCLC) continues to top the list of cancer mortalities worldwide. Early diagnosis and therapeutic interventions targeting NSCLC is becoming the world's significant challenge. Circular RNAs (circRNAs) are emerging as a group of potential cancer biomarkers. Materials and methods: Quantitative real-time PCR (qRT-PCR) was employed to examine the expression of circ 0072309 in NSCLC tissues and cell lines. Cell counting kit 8 (CCK-8), wound healing and Transwell assays were used to analyze cell proliferation, migration and invasion in A549 and H1299 cells. The relationship between circ 0072309 and miR-580-3 was analyzed by Luciferase reporter and RNA pull down assays. Results: We screened circ 0072309 from Gene Expression Omnibus and found that circ 0072309 was lowly expressed in NSCLC tissues and cell lines. The transfection of circ 0072309-overexpressing vector significantly suppressed the cell proliferation, migration and invasion in A549 and H1299 cells. We predicted that miR-580-3p is a target of circ 0072309 by using publicly available bioinformatic algorithms Circinteractome tool and confirmed that circ 0072309 directly bound to miR-580-3p. Furthermore, the addition of miR-580-3p mitigated the blockage of cell proliferation, migration and invasion induced by circ 0072309. Conclusions: These data showed that circ 0072309 inhibits the progression of NSCLC progression via blocking the expression of miR-580-3p. These findings revealed the anti-tumor role of circ 0072309 during the development of NSCLC and provided a novel diagnostic biomarker and potential therapy for NSCLC.

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Section: Discussionmentioning

confidence: 99%

Circular RNA hsa_circ_0072309 inhibits non-small cell lung cancer progression by sponging miR-580-3p

et al. 2020

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“…circHIPK3 (hsa_circ 0000284) is a circular RNA derived from the second exon of the HIPK3 gene. circHIPK3 is highly expressed in liver, brain, and lung (13)(14)(15) and has shown an important role in the regulation of cell survival, oxidative damage, and inflammation (16)(17)(18). We note that circHIPK3 is also expressed in pancreatic tissue (19).…”

Section: Introductionmentioning

confidence: 75%

CircHIPK3 Promotes Pyroptosis in Acinar Cells Through Regulation of the miR-193a-5p/GSDMD Axis

Wang

Liu

et al. 2020

Front. Med.

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Acute pancreatitis (AP), especially severe acute pancreatitis (SAP), is an extremely dangerous illness with a high mortality rate. Pyroptotic cells release their cellular contents and inflammatory factors, aggravating the inflammatory response. Pyroptosis may be the main mode of acinar cell death during AP. The circular RNA circHIPK3 is expressed in pancreatic tissue and is associated with inflammatory response. In this study, we focused on the role and underlying mechanism of circHIPK3 in AP. We found that the expression of circHIPK3 was significantly elevated in serum of patients with AP and in caerulein-stimulated AR42J cells and was associated with caspase-1 and caspase-11 activation. circHIPK3 silencing ameliorated caerulein-induced cell damage and reduced the release of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α and inhibited the activation of caspase-1 and caspase-11. In addition, circHIPK3 bound to miR-193a-5p and negatively regulated its expression. Inhibition of miR-193a-5p increased the release of IL-1β, IL-6, IL-8, and TNF-α and activated caspase-1 and caspase-11, thereby counteracting the effect of circHIPK3 silencing on caerulein-induced cell damage. Furthermore, we identified GSDMD as a target gene of miR-193a-5p, which is the key gene for pyroptosis. Interfering with the expression of GSDMD can increase cell viability, reduce the secretion of inflammatory cytokines, and suppress the activation of cleaved caspase-1 and caspase-11. Silencing GSDMD reversed the effects of miR-193a-5p inhibitors on caerulein-induced damage. In conclusion, circHIPK3 promotes pyroptosis in acinar cells through regulation of the miR-193a-5p/GSDMD axis, which eventually aggravates AP disease.

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“…Even though it is not deniable that CK2 plays a central role in cancer diseases it is likely that antiproliferative effects of silmitasertib (1) are also a consequence of inhibiting off-targets [29]. Main off-targets of silmitasertib (1) reported to have antiproliferative effects are for example the cyclin-dependent kinase (CDK1) [43,44], PIM-1 protooncogene, serine/threonine kinase (PIM1) [45], Homeodomain-interacting protein kinase 3 (HIPK3) [46,47], TANK-binding kinase 1 (TBK1) [48] or FMS-like tyrosine kinase 3 (FLT3) [49,50]. More recently some more selective CK2 inhibitors have been reported, including GO289 by Oshima et al [51] or an allosteric inhibitor CAM4066 by Brear et al [18].…”

Section: Conclusion/discussionmentioning

confidence: 99%

Optimization of pyrazolo[1,5-a]pyrimidines lead to the identification of a highly selective casein kinase 2 inhibitor

Kraemer

Kurz

Berger

et al. 2020

Preprint

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Casein kinase 2 (CK2) is a constitutively expressed serine/threonine kinase that has a large diversity of cellular substrates. Thus, CK2 has been associated with a plethora of regulatory functions and dysregulation of CK2 has been linked to disease development in particular to cancer. The broad implications in disease pathology makes CK2 an attractive target. To date, the most advanced CK2 inhibitor is silmitasertib, which has been investigated in clinical trials for treatment of various cancers, albeit several off-targets for silmitasertib have been described. To ascertain the role of CK2 inhibition in cancer, other disease and normal physiology the development of a selective CK2 inhibitor would be highly desirable. In this study we explored the pyrazolo[1,5-a]pyrimidine hinge-binding moiety for the development of selective CK2 inhibitors. Optimization of this scaffold, which included macrocyclization, led to IC20 (31) a compound that displayed high in vitro potency for CK2 (KD = 12 nM) and exclusive selectivity for CK2. X-ray analysis revealed a canonical type-I binding mode for IC20. However, the polar carboxylic acid moiety that is shared by many CK2 inhibitors including silmitasertib was required for potency and reduced somewhat cellular activity. In summary, IC20 represents a highly selective and potent inhibitor of CK2, which can be used as a tool compound to study CK2 biology and potential new applications for the treatment of diseases.

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Circular RNA HIPK3 induces cell proliferation and inhibits apoptosis in non-small cell lung cancer through sponging miR-149

Cited by 58 publications

References 19 publications

Circular RNA hsa_circ_0072309 inhibits non-small cell lung cancer progression by sponging miR-580-3p

Circular RNA hsa_circ_0072309 inhibits non-small cell lung cancer progression by sponging miR-580-3p

CircHIPK3 Promotes Pyroptosis in Acinar Cells Through Regulation of the miR-193a-5p/GSDMD Axis

Optimization of pyrazolo[1,5-a]pyrimidines lead to the identification of a highly selective casein kinase 2 inhibitor

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