ADAM17 Confers Temozolomide Resistance in Human Glioblastoma Cells and miR-145 Regulates Its Expression

Yang, Jen-Tsung; Lee, I‐Neng; Huang, Cheng; Huang, Han-Pang; Wu, Yuping; Chong, Zhi-Yong; Chen, Jui‐Chieh

doi:10.3390/ijms24097703

Cited by 5 publications

(5 citation statements)

References 58 publications

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“…2D ). During stressful conditions such as starvation or chemotherapy, cancer cells may activate certain signaling pathways that give them an advantage in survival ( 37 ). Therefore, U87MG and U87MGR cells were cultured in serum-free medium for 24 and 48 h and the changes in HGF expression and MET activation upon starvation were assessed.…”

Section: Resultsmentioning

confidence: 99%

“…To verify the present findings, another GBM cell line, DBTRG-05MG cells, were selected to investigate the effect of lidocaine on the MET pathway and further analyze its relationship with TMZ sensitivity and cell migration. This choice was based on a previous study by the authors, which revealed that DBTRG-05MG cells exhibit a high level of resistance to TMZ ( 37 ). The DBTRG-05MG cells were cultured in a serum-free medium for 24 and 48 h, and the impact of starvation on MET activation was evaluated using western blotting.…”

Section: Resultsmentioning

confidence: 99%

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Lidocaine attenuates TMZ resistance and inhibits cell migration by modulating the MET pathway in glioblastoma cells

Chen,

Chong,

Huang

et al. 2024

Oncol Rep

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Glioblastoma multiforme (GBM) is the most aggressive type of malignant brain tumor. Currently, the predominant clinical treatment is the combination of surgical resection with concurrent radiotherapy and chemotherapy, using temozolomide (TMZ) as the primary chemotherapy drug. Lidocaine, a widely used amide-based local anesthetic, has been found to have a significant anticancer effect. It has been reported that aberrant hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signaling plays a role in the progression of brain tumors. However, it remains unclear whether lidocaine can regulate the MET pathway in GBM. In the present study, the clinical importance of the HGF/MET pathway was analyzed using bioinformatics. By establishing TMZ-resistant cell lines, the impact of combined treatment with lidocaine and TMZ was investigated. Additionally, the effects of lidocaine on cellular function were also examined and confirmed using knockdown techniques. The current findings revealed that the HGF/MET pathway played a key role in brain cancer, and its activation in GBM was associated with increased malignancy and poorer patient outcomes. Elevated HGF levels and activation of its receptor were found to be associated with TMZ resistance in GBM cells. Lidocaine effectively suppressed the HGF/MET pathway, thereby restoring TMZ sensitivity in TMZ-resistant cells. Furthermore, lidocaine also inhibited cell migration. Overall, these results indicated that inhibiting the HGF/MET pathway using lidocaine can enhance the sensitivity of GBM cells to TMZ and reduce cell migration, providing a potential basis for developing novel therapeutic strategies for GBM.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Lidocaine attenuates TMZ resistance and inhibits cell migration by modulating the MET pathway in glioblastoma cells

Chen,

Chong,

Huang

et al. 2024

Oncol Rep

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“…Furthermore, ADAM17 is responsible for pathological and physiological processes, such as cell growth, inflammation, differentiation, regeneration, and tumor progression [ 97 ]. It was identified that miR-145-5p increased TMZ sensitivity in GBM cells by ADAM17 targeting [ 99 ].…”

Section: Wnt/β-catenin and Pi3k/akt Signaling Pathwaysmentioning

confidence: 99%

MicroRNAs as the pivotal regulators of Temozolomide resistance in glioblastoma

Palizkaran Yazdi,

Barjasteh,

Moghbeli

2024

Mol Brain

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Glioblastoma (GBM) is an aggressive nervous system tumor with a poor prognosis. Although, surgery, radiation therapy, and chemotherapy are the current standard protocol for GBM patients, there is still a poor prognosis in these patients. Temozolomide (TMZ) as a first-line therapeutic agent in GBM can easily cross from the blood-brain barrier to inhibit tumor cell proliferation. However, there is a high rate of TMZ resistance in GBM patients. Since, there are limited therapeutic choices for GBM patients who develop TMZ resistance; it is required to clarify the molecular mechanisms of chemo resistance to introduce the novel therapeutic targets. MicroRNAs (miRNAs) regulate chemo resistance through regulation of drug metabolism, absorption, DNA repair, apoptosis, and cell cycle. In the present review we discussed the role of miRNAs in TMZ response of GBM cells. It has been reported that miRNAs mainly induced TMZ sensitivity by regulation of signaling pathways and autophagy in GBM cells. Therefore, miRNAs can be used as the reliable diagnostic/prognostic markers in GBM patients. They can also be used as the therapeutic targets to improve the TMZ response in GBM cells.

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“…In recent years, many studies focused on the regulatory role of miRNAs as the core of the competitive endogenous RNA (ceRNA) hypothesis that explains the relationship between different classes of RNAs including circRNA, long noncoding RNA (lncRNA), miRNAs and mRNAs 9 . Hsa-miR-145-5p , one of the targets of several dysregulated circRNAs identified in studies, has been widely confirmed to be associated with cancer 8 , 10 . Evidence has shown that miR-145-5p can be regulated by different mechanisms and can involve in tumorigenesis and progression through binding to 3′-UTRs of target mRNAs 10 , 11 .…”

Section: Introductionmentioning

confidence: 98%

“…Hsa-miR-145-5p , one of the targets of several dysregulated circRNAs identified in studies, has been widely confirmed to be associated with cancer 8 , 10 . Evidence has shown that miR-145-5p can be regulated by different mechanisms and can involve in tumorigenesis and progression through binding to 3′-UTRs of target mRNAs 10 , 11 . Several studies have reported that miR-145-5p can significantly suppress tumor progression, including in colorectal cancer (CRC) 12 , lung cancer 13 , and glioma 14 via targeting epidermal growth factor receptor (EGFR) gene.…”

Section: Introductionmentioning

confidence: 98%

CircZNF609 and circNFIX as possible regulators of glioblastoma pathogenesis via miR-145-5p/EGFR axis

Ghadami,

Gorji,

Pour-Rashidi

et al. 2024

Sci Rep

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Glioblastoma is a rare and deadly malignancy with a low survival rate. Emerging evidence has shown that aberrantly expressed circular RNAs (circRNAs) play a critical role in the initiation and progression of GBM tumorigenesis. The oncogenic function of circZNF609 and circNFIX is involved in several types of cancer, but the role and underlying mechanism of these circRNAs in glioblastoma remain unclear. In this study, we hypothesized that circZNF609 and circNFIX may regulate EGFR through sponging miR-145-5p. Herein, we assessed the expression levels of circZNF609, circNFIX, miR-145-5p, and EGFR using quantitative polymerase chain reaction in glioblastoma patients and normal brain samples. The results showed that circZNF609, circNFIX, and EGFR expression levels were upregulated and miR145-5p was downregulated (p = 0.001, 0.06, 0.002, and 0.0065, respectively), while there was no significant association between clinicopathological features of the patients and the level of these genes expression. We also found a significant inverse correlation between miR145-5p and the expression of cZNF609, cNFIX and EGFR (p = 0.0003, 0.0006, and 0.009, respectively). These findings may open a new window for researchers to better understand the potential pathways involved in GBM pathogenesis. In conclusion, it may provide a new potential pathway for the development of effective drugs for the treatment of GBM patients.

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ADAM17 Confers Temozolomide Resistance in Human Glioblastoma Cells and miR-145 Regulates Its Expression

Cited by 5 publications

References 58 publications

Lidocaine attenuates TMZ resistance and inhibits cell migration by modulating the MET pathway in glioblastoma cells

Lidocaine attenuates TMZ resistance and inhibits cell migration by modulating the MET pathway in glioblastoma cells

MicroRNAs as the pivotal regulators of Temozolomide resistance in glioblastoma

CircZNF609 and circNFIX as possible regulators of glioblastoma pathogenesis via miR-145-5p/EGFR axis

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