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Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib has exhibited notable clinical efficacy in non-small cell lung cancer (NSCLC) patients. However, its therapeutic efficacy is ultimately limited by the development of gefitinib resistance. The present study aimed to investigate the effects of the long non-coding RNA, RHPN1-AS1 on gefitinib resistance in NSCLC and explore the underlying mechanisms. In this study, RHPN1-AS1 was observed to be downregulated in gefitinib resistant patients and NSCLC cell lines. Besides, decreased expression of RHPN1-AS1 was found to be associated with poor prognosis of NSCLC patients. RHPN1-AS1 knockdown conferred gefitinib resistance to gefitinib sensitive NSCLC cells, whereas the overexpression of RHPN1-AS1 sensitized gefitinib resistant NSCLC cells to gefitinib treatment. Mechanistically, RHPN1-AS1 was found to positively regulate the expression of TNFSF12 by directly interacting with miR-299-3p. Collectively, RHPN1-AS1 modulates gefitinib resistance through miR-299-3p/TNFSF12 pathway in NSCLC. Our findings indicate that RHPN1-AS1 may serve as not only a prognostic biomarker for gefitinib resistance but also as a promising therapeutic biomarker and target for the treatment of NSCLC patients.
This article was published in the following journal.
Name: Cell cycle (Georgetown, Tex.)
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Precision medicine has made a significant breakthrough in the past decade. The most representative success is the molecular targeting therapy of epidermal growth factor receptor (EGFR) tyrosine kinase...
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A cytoplasmic receptor and peroxin that contains a series of TETRACOTIPEPTIDE REPEATS and binds to PEROXISOME TARGETING SIGNAL 1 (SKL-type). It is essential for protein import into PEROXISOMES; mutations in the PEX5 gene are associated with PEROXISOMAL DISORDERS such as ZELLWEGER SYNDROME.
A cytoplasmic receptor and peroxin that contains a series of WD40 REPEATS and binds to PEROXISOME TARGETING SIGNAL 2. It is essential for protein import into PEROXISOMES; mutations in the human PEX7 gene are associated with PEROXISOMAL DISORDERS such as Type 1 CHONDRODYSPLASIA PUNCTATA, RHIZOMELIC.
A type of strength-building exercise program that requires the body muscle to exert a force against some form of resistance, such as weight, stretch bands, water, or immovable objects. Resistance exercise is a combination of static and dynamic contractions involving shortening and lengthening of skeletal muscles.
The development by insects of resistance to insecticides.
Simultaneous resistance to several structurally and functionally distinct drugs.
GILOTRIF (afatinib) is a kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L8...