RAS-MAPK signaling influences the efficacy of ALK-targeting agents in lung cancer

Hrustanovic, Gorjan; Bivona, Trever G.

doi:10.1080/23723556.2015.1091061

Cited by 8 publications

(8 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…33 Deregulation of the Ras-MAPK pathway is an early event in diverse cancers and functions as an important contributor to chemoresistance. 34 In basal cell carcinoma, activation of the RAS/MAPK signaling pathway repressed Shh signaling and reduced the sensitivity of basal cell carcinoma cells to smoothened inhibitor. 35 In the present study, NEAT1 was demonstrated to interact with let-7a-5p.…”

Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1/let-7a-5p axis regulates the cisplatin resistance in nasopharyngeal carcinoma by targeting Rsf-1 and modulating the Ras-MAPK pathway

Liu

Tai

2018

Cancer Biology & Therapy

View full text Add to dashboard Cite

The long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) was reported to be upregulated and be involved in oncogenic growth and drug resistance in nasopharyngeal carcinoma (NPC). However, the exact roles of NEAT1 and its underlying mechanisms in the drug resistance of NPC remain largely unclear. In this study, the expressions of NEAT1, let-72-5p and Rsf-1 mRNA were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of NEAT1 and let-72-5p on cell proliferation and cisplatin resistance of NPC cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and 5-ethynyl-20-deoxyuridine (EdU) assay. Western blot analysis was performed to detect the protein levels of Rsf-1, Ras, p-Raf1, Raf1, p-MEK1, MEK1, p-ERK1/2 and ERK1/2. Xenograft tumor assay was done to elucidate the role of NEAT1 involved in NPC tumor growth in vivo. We found that NEAT1 was upregulated and let-7a-5p was downregulated in NPC tissues, as well as NPC cell lines. Inhibition of NEAT1 markedly repressed the cisplatin resistance of NPC cells. NEAT1 was demonstrated to interact with let-7a-5p. Besides, a negative correlation between NEAT1 and let-7a-5p expression was observed in NPC tissues. Rsf-1 was confirmed as a target of let-7a-5p. NEAT1 remarkably reversed the inhibitory effect of let-7q-5p on the cisplatin resistance of NPC cells in vitro. Additionally, NEAT1 knockdown inhibited the Ras-MAPK pathway in NPC cells. NEAT1 knockdown suppressed tumor growth in the presence of cisplatin in vivo. Overall, these findings suggest that NEAT1/let-7a-5p axis regulates the cisplatin resistance in NPC by targeting Rsf-1 and modulating the Ras-MAPK signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1/let-7a-5p axis regulates the cisplatin resistance in nasopharyngeal carcinoma by targeting Rsf-1 and modulating the Ras-MAPK pathway

Liu

Tai

2018

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

“…report an upregulation of NEAT1 in cancer tissue and NPC cell lines and showed that knockdown of this lncRNA leads to inhibited proliferation, chemoresistance, and induced apoptosis (Cheng and Guo, ; Liu et al ., 2018a). Increased NEAT1 levels found in NPC tissue and cells negatively correlated with expression levels of the tumor‐suppressive (Sampson et al ., ) miRNA let‐7a‐5p resulting in upregulation of the oncogenic (Hrustanovic and Bivona, ) Ras‐MAPK‐signaling pathway; thus, authors conclude a contribution of the NEAT1/let‐7a‐5p axis to chemoresistance in NPC by modulation of Ras‐MAPK signaling (Liu et al ., 2018a). Chen et al .…”

Section: Neat1 In Cancer Biologymentioning

confidence: 99%

Involvement of the long noncoding RNA NEAT1 in carcinogenesis

2018

View full text Add to dashboard Cite

Altered expression levels of the long noncoding RNA (lncRNA) nuclear‐enriched abundant transcript 1 (NEAT1) have been reported in different types of cancer. More than half of the NEAT1 studies in cancer have been published within the last 2 years. In this review, we discuss very recent developments and insights into NEAT1 contribution to carcinogenesis. Summarizing the literature, it becomes obvious that NEAT1 is a lncRNA highly de‐/upregulated in a variety of cancer entities, in which it primarily acts as a competing endogenous RNA (ceRNA) which sponges tumor‐suppressive microRNA (miRNA). The sponged miRNA lose their ability to degrade, silence, or hamper translation of their downstream—mostly oncogenic—target transcripts, ultimately promoting carcinogenesis. This role of NEAT1 function in tumorigenesis suggests it may be a prognostic biomarker as well as potential therapeutic target, pending the completion of further studies into the underlying mechanisms.

show abstract

“…In spite of the remarkable responses have been observed by some researchers [ 13 , 14 ], it is still controversy about the efficacy of ALK inhibitor in ALK-rearranged squamous cell carcinoma [ 9 ]. A recent study indicated that the RAS-RAF-MEK-ERK signaling pathway determines the ALK inhibitor response in ALK-positive lung cancer, but still needs further investigation [ 15 ]. In our case, the postoperative pathology revealed that the squamous cell carcinoma suffered from ALK fusion mutation.…”

Section: Discussionmentioning

confidence: 99%

Different driver gene mutations in patients with synchronous multiple primary lung cancers: a case report

Yang

Xie

Jiang

et al. 2020

J Cardiothorac Surg

View full text Add to dashboard Cite

Background Routine clinical and pathological examinations usually cannot fully conclusively determine the relationship between different lesions of lung cancer. Detailed genetic analysis of tumor samples may supply important additional information and identify second primary lung cancers. Case presentation In the present study, we report a case of synchronous multiple primary lung cancer (MPLC) composed of two distinct pathological subtypes with epidermal growth factor receptor (EGFR) gene mutations L858R of the acinar adenocarcinoma subtype and EML4–ALK rearrangement of the squamous cell carcinoma. Conclusion The present report highlights the clinical importance of molecular cancer biomarkers detection to guide management decisions in MPLC cases.

show abstract

RAS-MAPK signaling influences the efficacy of ALK-targeting agents in lung cancer

Cited by 8 publications

References 6 publications

LncRNA NEAT1/let-7a-5p axis regulates the cisplatin resistance in nasopharyngeal carcinoma by targeting Rsf-1 and modulating the Ras-MAPK pathway

LncRNA NEAT1/let-7a-5p axis regulates the cisplatin resistance in nasopharyngeal carcinoma by targeting Rsf-1 and modulating the Ras-MAPK pathway

Involvement of the long noncoding RNA NEAT1 in carcinogenesis

Different driver gene mutations in patients with synchronous multiple primary lung cancers: a case report

Contact Info

Product

Resources

About