Potential Molecular Targets in the Treatment of Lung Cancer Using siRNA Technology

Zarredar, Habib; Ansarin, Khalil; Baradaran, Behzad; Khosroshahi, Shiva Ahdi

doi:10.1080/07357907.2017.1416393

Cited by 19 publications

(19 citation statements)

References 156 publications

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“…Lung cancer has been the leading cause of cancer-related mortality since 1985, with over a million deaths each year worldwide. 1 In 2018, it is estimated that there were approximately 234 030 new cases and 154 050 lung cancer deaths in the United States (https://seer.cancer.gov/statfacts/html/ lungb.html). Non-smallcell lung cancer (NSCLC) is the most common histological type of lung cancer, accounting for approximately 80% to 85% of all lung cancer cases diagnosed.…”

Section: Introductionmentioning

confidence: 99%

Novel genetic variants in HDAC2 and PPARGC1A of the CREB‐binding protein pathway predict survival of non‐small‐cell lung cancer

Tang

Zhao

Qian

et al. 2019

Molecular Carcinogenesis

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The CREB-binding protein (CBP) pathway plays an important role in transcription and activity of acetyltransferase that acetylates lysine residues of histones and nonhistone proteins. In the present study, we hypothesized that genetic variants in the CBP pathway genes played a role in survival of non-small-cell lung cancer (NSCLC). We tested this hypothesis using the genotyping data from the genomewide association study (GWAS) dataset from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. In the single-locus analysis, we evaluated associations between 13 176 (1107 genotyped and 12 069 imputed) singlenucleotide polymorphisms (SNPs) in 72 genes and survival of 1185 patients with NSCLC. The identified 106 significant SNPs in the discovery were further validated in additional genotyping data from another GWAS dataset of 984 patients with NSCLC in the Harvard Lung Cancer Susceptibility Study. The combined results of two datasets showed that two independent, potentially functional SNPs (i.e., HDAC2 rs13213007G>A and PPARGC1A rs60571065T>A) were significantly associated with NSCLC overall survival, with a combined hazards ratio (HR) of 1.26 (95% confidence interval (CI), 1.09-1.45; P = .002) and1.23 (1.04-1.47; P = .017), respectively. Furthermore, we performed an expression

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Section: Introductionmentioning

confidence: 99%

Novel genetic variants in HDAC2 and PPARGC1A of the CREB‐binding protein pathway predict survival of non‐small‐cell lung cancer

Tang

Zhao

Qian

et al. 2019

Molecular Carcinogenesis

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“…For this reason, to decrease the mortality of lung cancer, the detection of lung cancer in the early stages can improve a patient's survival. Therefore, specific biomarkers could be very helpful in the early detection of lung cancer 4,5 . Many studies have shown microRNAs can be powerful biomarkers for the detection of lung cancer, particularly miRNA signatures, which are consisting of multiple markers.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, specific biomarkers could be very helpful in the early detection of lung cancer. 4,5 Many studies have shown microRNAs can be powerful biomarkers for the detection of lung cancer, particularly miRNA signatures, which are consisting of multiple markers. Until now, the diagnostic power of long noncoding RNA (lncRNA) signatures for lung cancer detection has not been evaluated sufficiently.…”

Section: Introductionmentioning

confidence: 99%

Long non‐coding RNAs as potential biomarkers in the prognosis and diagnosis of lung cancer: A review and target analysis

et al. 2020

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Long non-coding RNAs (lncRNA) have been emerged as a novel class of molecular regulators in cancer. They are dysregulated in many types of cancer; however, there is not enough knowledge available on their expression and functional profiles. Lung cancer is the leading cause of the cancer deaths worldwide. Generally, lncRNAs may be associated with lung tumor pathogenesis and they may act as biomarkers for the cancer prognosis and diagnosis. Compared to other invasive prognostic and diagnostic methods, detection of lncRNAs might be a user-friendly and noninvasive method. In this review article, we selected 27 tumor-associated lncRNAs by literature reviewing to further discussing in detail for using as diagnostic and prognostic biomarkers in lung cancer. Also, in an in silico target analysis, the "Experimentally supported functional regulation" approach of the LncTarD web tool was used to identifying the target genes and regulatory mechanisms of the selected lncRNAs. The reports on diagnostic and prognostic potential of all selected lncRNAs were discussed. However, the target genes and regulatory mechanisms of the 22 lncRNAs were identified by in silico analysis and we found the pathways that are controlled by each target group of lncRNAs. They use epigenetic mechanisms, ceRNA mechanisms, protein interaction and sponge mechanism. Also, 10, 23, 5, and 28 target genes for each of these mechanisms were identified, respectively. Finally, each group of target genes controls 50, 12, 7, and 2 molecular pathways, respectively. In conclusion, LncRNAs could be used as

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“…It has been shown that patients with EGFR mutations develop an acquired resistance against tyrosine kinase inhibitors (TKIs; Jackman et al, 2010). RAS is a downstream molecule of EGFR, and KRAS overexpression leads to resistance to EGFR TKI in tumors (Tammemagi, McLaughlin, & Bull, 1999;Zarredar, Ansarin, Baradaran, Ahdi Khosroshahi, & Farajnia, 2018a).…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that patients with EGFR mutations develop an acquired resistance against tyrosine kinase inhibitors (TKIs; Jackman et al, ). RAS is a downstream molecule of EGFR, and KRAS overexpression leads to resistance to EGFR TKI in tumors (Tammemagi, McLaughlin, & Bull, ; Zarredar, Ansarin, Baradaran, Ahdi Khosroshahi, & Farajnia, ). Tumors with KRAS mutation seem to be resistant to most available systemic therapies, making KRAS as a critical target for cancer therapy (Koivunen et al, ).…”

Section: Introductionmentioning

confidence: 99%

Combination therapy with KRAS siRNA and EGFR inhibitor AZD8931 suppresses lung cancer cell growth in vitro

Zarredar

Pashapour

Ansarin

et al. 2018

Journal Cellular Physiology

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Lung cancer is a leading cause of cancer-related deaths worldwide, with less than a 5-year survival rate for both men and women. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma oncogene (KRAS) signaling pathways play a critical role in the proliferation and progression of various cancers, including lung cancer. Genetic studies have shown that amplification, over-expression, or mutation of EGFR is an early and major molecular event in many human tumors. KRAS mutation is a negative factor in various cancer, including non-small-cell lung cancer, and complicates therapeutic approaches with adjuvant chemotherapy and anti-EGFR directed therapies. This article is dedicated to evaluating the synergistic effect of a novel EGFR inhibitor AZD8931 and KRAS small interfering RNA (siRNA) on the proliferation and apoptosis of lung adenocarcinoma cancer cells. A549 lung cancer cells were treated with KRAS siRNA and the EGFR inhibitor alone or in combination. The cytotoxic effects of KRAS siRNA and te EGFR inhibitor were determined usingMTT assay, and induction of apoptosis was determined by FACS analysis. Suppression of KRAS, Her-2, and EGFR expression by treatments was measured by qRT-PCR and western blotting. KRAS siRNA and the EGFR inhibitor significantly reduced the proliferation of A549 cells as well as KRAS and EGFR mRNA levels 24 hr after treatment. The results also indicated that the silencing of KRAS and EGFR has synergistic effects on the induction of apoptosis on the A549 cells. These results indicated that KRAS and EGFR might play important roles in the progression of lung cancer and could be potential therapeutic targets for treatment of lung cancer.

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Potential Molecular Targets in the Treatment of Lung Cancer Using siRNA Technology

Cited by 19 publications

References 156 publications

Novel genetic variants in HDAC2 and PPARGC1A of the CREB‐binding protein pathway predict survival of non‐small‐cell lung cancer

Novel genetic variants in HDAC2 and PPARGC1A of the CREB‐binding protein pathway predict survival of non‐small‐cell lung cancer

Long non‐coding RNAs as potential biomarkers in the prognosis and diagnosis of lung cancer: A review and target analysis

Combination therapy with KRAS siRNA and EGFR inhibitor AZD8931 suppresses lung cancer cell growth in vitro

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