MiR‐873 inhibition enhances gefitinib resistance in non‐small cell lung cancer cells by targeting glioma‐associated oncogene homolog 1

Jin, Shidai; He, Jing; Li, Jun; Guo, Renhua; Shu, Yongqian; Liu, Ping

doi:10.1111/1759-7714.12830

Cited by 26 publications

(25 citation statements)

References 48 publications

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“…In our work, we proved that miR-873 was a direct target of circDGKB, and inhibition of the expression of miR-873 enhanced the proliferation, migration, invasion, and S phase arrest of SK-N-SH cells and reduced cell apoptosis. This results were consistent with previous studies, which indicated the suppressive role of miR-873 in cancers including CRC (38,39), breast cancer (40), NSCLC (41), and gastric cancer (42). Furthermore, we found that miR-873 overexpression significantly rescued circDGKB role in promoting NB progression, illustrating that circDGKB promoted NB progression by targeting miR-873.…”

Section: Discussionsupporting

confidence: 93%

Circular RNA DGKB Promotes the Progression of Neuroblastoma by Targeting miR-873/GLI1 Axis

Yang

Yan

et al. 2020

Front. Oncol.

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Accumulated evidences suggested that circular RNAs (circRNA) played critical roles in tumorigenesis and progression. To our knowledge, no study reported the function of circular RNA DGKB (circDGKB, circRNA ID: hsa_circ_0133622) on progression of neuroblastoma (NB). Here, we showed that circDGKB was upregulated in NB tissues compared to the normal dorsal root ganglia. Moreover, the expression level of circDGKB was negatively correlated with the survival rate of NB patients. Mechanically, overexpression of circDGKB promoted the proliferation, migration, invasion, and tumorigenesis of NB cells and reduced cell apoptosis, and vice versa. In addition, qRT-PCR and/or Western blot results showed that circDGKB overexpression inhibited the expression level of miR-873 and enhanced GLI1 expression. Moreover, miR-873 functioned an opposite role to circDGKB and significantly weakened circDGKB role in promoting NB progression. Furthermore, GLI1 upregulation also rescued the miR-873 role in inhibiting NB progression. In conclusion, our work proved that circDGKB promoted NB progression via targeting miR-873/GLI1 axis in vitro and in vivo. Our study provided a new target for NB treatment and indicated that circDGKB could act as a novel diagnostic marker for NB.

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Section: Discussionsupporting

confidence: 93%

Circular RNA DGKB Promotes the Progression of Neuroblastoma by Targeting miR-873/GLI1 Axis

Yang

Yan

et al. 2020

Front. Oncol.

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“…Similarly, Bai et al (67) reported that A549 and H1975 cells, which had high levels of GLI1 expression, were resistant to another EGFR TKI, gefitinib, and the use of the SMO inhibitor, SANT-1, showed a synergistic effect with gefitinib in A549 and H1975 cell lines. Recently, it was reported that the downregulation of GLI1 using microRNA-873 in the PC9 lung cancer cell line enhanced its sensitivity to gefitinib (68), which is consistent with the current study. In the future, with the development of safe and efficient GLI1 inhibitors, combination treatment of different EGFR-TKIs and GLI inhibitors may be investigated.…”

Section: Gene -------------------------------------------------------supporting

confidence: 93%

GLI1 activation is a key mechanism of erlotinib resistance in human non‑small cell lung cancer

et al. 2020

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Lung cancer is the leading cause of cancer-associated death worldwide. In recent years, the advancement of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted therapies has provided clinical benefits for lung cancer patients with EGFR mutations. The response to EGFR-TKI varies in patients with lung cancer, and resistance typically develops during the course of the treatment. Therefore, understanding biomarkers which can predict resistance to EGFR-TKI is important. Overexpression of GLI causes activation of the Hedgehog (Hh) signaling pathway and plays a critical role in oncogenesis in numerous types of cancer. In the present study, the role of GLI1 in erlotinib resistance was investigated. GLI1 mRNA and protein expression levels were determined using reverse transcription-quantitative PCR and immunohistochemistry (IHC) in lung cancer cell lines and tumor specimens, respectively. GLI1 mRNA expression levels were found to be positively correlated with the IC 50 of erlotinib in 15 non-small cell lung cancer (NSCLC) cell lines. The downregulation of GLI1 using siRNA sensitized lung cancer cells to the erlotinib treatment, whereas the overexpression of GLI1 increased the survival of lung cancer cells in the presence of erlotinib, indicating that Hh/GLI activation may play a critical role in the development of TKI resistance in lung cancer. Combined treatment with erlotinib and a GLI1 inhibitor reduced the cell viability synergistically. A retrospective study of patients with NSCLC treated with erlotinib revealed that those with a high IHC score for GLI1 protein expression had a poorer prognosis. These results indicated that GLI1 is a key regulator for TKI sensitivity, and patients with lung cancer may benefit from the combined treatment of TKI and GLI1 inhibitor.

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“…MiR-608 and miR-4513 can enhance the sensitivity of NSCLC cells, such as PC-9 cells, to gefitinib [159]. MiR-873 confers sensitivity to gefitinib in NSCLC cells by targeting glioma-associated oncogene homolog 1 [160]. MiR-483-3p can enhance the sensitivity of NSCLC cells to gefitinib by increasing autophagy and apoptosis [161].…”

Section: Mirnas Regulate Response Of Cancer Cells To Anti-egfr Trementioning

confidence: 99%

Targeting Autophagy for Overcoming Resistance to Anti-EGFR Treatments

Kwon

Kim

Jung

et al. 2019

Cancers

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Epidermal growth factor receptor (EGFR) plays critical roles in cell proliferation, tumorigenesis, and anti-cancer drug resistance. Overexpression and somatic mutations of EGFR result in enhanced cancer cell survival. Therefore, EGFR can be a target for the development of anti-cancer therapy. Patients with cancers, including non-small cell lung cancers (NSCLC), have been shown to response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and anti-EGFR antibodies. However, resistance to these anti-EGFR treatments has developed. Autophagy has emerged as a potential mechanism involved in the acquired resistance to anti-EGFR treatments. Anti-EGFR treatments can induce autophagy and result in resistance to anti-EGFR treatments. Autophagy is a programmed catabolic process stimulated by various stimuli. It promotes cellular survival under these stress conditions. Under normal conditions, EGFR-activated phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling inhibits autophagy while EGFR/rat sarcoma viral oncogene homolog (RAS)/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) signaling promotes autophagy. Thus, targeting autophagy may overcome resistance to anti-EGFR treatments. Inhibitors targeting autophagy and EGFR signaling have been under development. In this review, we discuss crosstalk between EGFR signaling and autophagy. We also assess whether autophagy inhibition, along with anti-EGFR treatments, might represent a promising approach to overcome resistance to anti-EGFR treatments in various cancers. In addition, we discuss new developments concerning anti-autophagy therapeutics for overcoming resistance to anti-EGFR treatments in various cancers.

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MiR‐873 inhibition enhances gefitinib resistance in non‐small cell lung cancer cells by targeting glioma‐associated oncogene homolog 1

Cited by 26 publications

References 48 publications

Circular RNA DGKB Promotes the Progression of Neuroblastoma by Targeting miR-873/GLI1 Axis

Circular RNA DGKB Promotes the Progression of Neuroblastoma by Targeting miR-873/GLI1 Axis

GLI1 activation is a key mechanism of erlotinib resistance in human non‑small cell lung cancer

Targeting Autophagy for Overcoming Resistance to Anti-EGFR Treatments

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