Targeting EphA2 with miR-124 mediates Erlotinib resistance in <i>K-RAS</i> mutated pancreatic cancer

Du, Jing; He, Yakun; Wu, Weiquan; Chen, You‐Wei; Hu, Zhiming; Han, Yong

doi:10.1111/jphp.12941

Cited by 26 publications

(20 citation statements)

References 28 publications

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“…As overexpressing EphA2 could promote drug resistance to erlotinib in BXPC-3 cells, miR-124 might function as a drug-sensitive enhancer to improve pancreatic cancer patient clinical outcomes. 65 These explanations demonstrate that miR-124 has a strong association with the occurrence, progression, and prognosis of pancreatic cancer, suggesting that miR-124 also plays a similar role as tumor suppressor genes in pancreatic cancer. However, different reports of miR-124 are still emerging.…”

Section: Mir-124 and Pancreatic Cancermentioning

confidence: 95%

“…In addition, EphA2 (erythropoietin‐producing hepatocellular receptor 2) was shown to be another regulatory downstream gene of miR‐124. As overexpressing EphA2 could promote drug resistance to erlotinib in BXPC‐3 cells, miR‐124 might function as a drug‐sensitive enhancer to improve pancreatic cancer patient clinical outcomes …”

Section: Mir‐124 and Pancreatic Cancermentioning

confidence: 99%

“…They also showed that the downstream target gene of miR‐124 was SGK1. In addition, their findings suggested that XIST and miR‐124 may be ideal therapeutic targets to promote the DOX‐based chemotherapy effect in CRC …”

Section: Mir‐124 and Colorectal Cancermentioning

confidence: 99%

“…In addition, their findings suggested that XIST and miR-124 may be ideal therapeutic targets to promote the DOX-based chemotherapy effect in CRC. 65 Briefly, miR-124 exerts a tumor suppressor role by targeting its downstream genes during the development of CRC. In particular, miR-124 could serve as a powerful diagnostic and therapeutic tool for CRC.…”

Section: Mir-124 and Colorectal Cancermentioning

confidence: 99%

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MicroRNA‐124: An emerging therapeutic target in cancer

et al. 2019

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MicroRNAs (miRNAs) are noncoding single‐stranded RNAs, approximately 20‐24 nucleotides in length, known as powerful posttranscriptional regulators. miRNAs play important regulatory roles in cellular processes by changing messenger RNA expression and are widely involved in human diseases, including tumors. It has been reported in the literature that miRNAs have a precise role in cell proliferation, programmed cell death, differentiation, and expression of coding genes. MicroRNA‐124 (miR‐124) has reduced exparession in various human neoplasms and is believed to be related to the occurrence, development, and prognosis of malignant tumors. In our review, we focus on the specific molecular functions of miR‐124 and the downstream gene targets in major cancers, which provide preclinical evidence for the treatment of human cancer. Although some obstacles exist, miR‐124 is still attracting intensive research focus as a promising and effective anticancer weapon.

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Section: Mir-124 and Pancreatic Cancermentioning

confidence: 95%

Section: Mir‐124 and Pancreatic Cancermentioning

confidence: 99%

Section: Mir‐124 and Colorectal Cancermentioning

confidence: 99%

Section: Mir-124 and Colorectal Cancermentioning

confidence: 99%

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MicroRNA‐124: An emerging therapeutic target in cancer

et al. 2019

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“…Jing et al reported that erythropoietin-producing hepatocellular receptor 2 (EphA2), rescued by miR-124 downregulation, conferred erlotinib resistance in pancreatic cancer cells Capan-1, which contain a mutated copy of K-RAS [14]. However, none of these attempts have succeeded clinically thus far.…”

Section: Discussionmentioning

confidence: 99%

Silencing of the DJ-1 (PARK7) gene sensitizes pancreatic cancer to erlotinib inhibition

Sun

Fan

et al. 2019

Preprint

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AIMS: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib, in combination with gemcitabine, has been shown to be a promising therapy in the treatment of pancreatic cancer. Our previous study showed that DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/uPA. The aim of this study was to evaluate whether silencing DJ-1 expression can sensitize pancreatic cancer cells to erlotinib treatment. METHODS: Knockdown of DJ-1 expression, combined with erlotinib treatment, was performed in the pancreatic cancer cell lines BxPC-3 and PANC-1. Cell proliferation was assessed with the CCK-8 assay and BrdU incorporation, while apoptosis was measured using terminal deoxynucleotidyl ransferase (TdT)-mediated dUTP nick-end labeling. RAS activity and activation of the downstream pathways involving AKT and ERK1/2 were explored to determine the underlying mechanism. RESULTS: Knockdown of DJ-1 expression accelerated erlotinib-induced cell apoptosis, and improved the inhibitory effect of erlotinib on pancreatic cancer cell proliferation in vitro and in xenograft tumor growth in vivo. Knockdown of DJ-1 decreased K-RAS expression, membrane translocation, and activity in BxPC-3 cells. Knockdown of DJ-1 also decreased K-RAS, H-RAS, and N-RAS expression in PANC-1 cells. Knockdown of DJ-1 synergistically inhibited AKT and ERK1/2 phosphorylation with erlotinib in pancreatic cancer cells. CONCLUSIONS: DJ-1 may activate the RAS pathway, reinforcing erlotinib drug resistance. Blocking DJ-1 in combination with the EGFR tyrosine kinase inhibitor erlotinib may be an attractive therapeutic target in pancreatic cancer.

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Combination of two miRNAs has a stronger effect on stimulating apoptosis, inhibiting cell growth, and increasing erlotinib sensitivity relative to single miRNA in A549 lung cancer cells

Amri

Molaee

Karami

et al. 2021

Biotech and App Biochem

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Despite the dramatic efficacy of EGFR‐TKIs, most of non‐small cell lung cancer patients ultimately develop resistance to these agents. In this study, we explored the effects of miRNA‐125a‐5p and miRNA‐145, alone or in combination, EGFR expression, cell growth and sensitivity of the NSCLC cells to erlotinib. The expression of EGFR was measured using RT‐qPCR and Western blotting. The effect of miRNAs and erlotinib on cell growth and survival was assessed by trypan blue assay and MTT assay, respectively. Apoptosis was measured using ELISA cell death assay. We found that transfection of miRNA‐125a‐5p and miRNA‐145 significantly inhibited the expression of EGFR mRNA and protein in a time‐dependent manner (p < 0.05 vs. blank control or negative control miRNA). ANOVA and Bonferroni's test were used to ascertain significant differences between groups. Other experiments indicated that upregulation of each of miRNA‐125a‐5p or miRNA‐145 inhibited cell growth, induced apoptosis, and markedly decreased the IC50 value of erlotinib in A549 lung cancer cells (p < 0.05). Moreover, the combination of two miRNAs showed a stronger effect on cells survival, apoptosis, and drug sensitivity, relative to single miRNA (p < 0.05). The results of our study indicate that the therapeutic delivery of miRNA‐145 and miRNA‐125a‐5p to lung cancer may inhibit cell proliferation, trigger apoptosis, and sensitize lung cancer cells to EGFR‐TKIs.

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Targeting EphA2 with miR-124 mediates Erlotinib resistance in K-RAS mutated pancreatic cancer

Cited by 26 publications

References 28 publications

MicroRNA‐124: An emerging therapeutic target in cancer

MicroRNA‐124: An emerging therapeutic target in cancer

Silencing of the DJ-1 (PARK7) gene sensitizes pancreatic cancer to erlotinib inhibition

Combination of two miRNAs has a stronger effect on stimulating apoptosis, inhibiting cell growth, and increasing erlotinib sensitivity relative to single miRNA in A549 lung cancer cells

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