MicroRNAs as Therapeutic Targets for Anticancer Drugs in Lung Cancer Therapy

Liu, Yuanrong; Wang, Pingyu; Xie, Ning; Xie, Shengsong

doi:10.2174/1871520620666200615133011

Cited by 4 publications

(4 citation statements)

References 155 publications

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“…Although their definite role in targeted treatment is not yet clear, miRNAs can alter tumor sensitivity to antitumor drugs ( Liu et al, 2020 ). A number of studies have shown that some antitumor drugs exert their antitumor effect via affecting miRNAs and their targeted genes.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR-185-3p Confers Erlotinib Resistance Through Upregulation of PFKL/MET in Lung Cancers

Zhu

Yuan

2021

Front. Cell Dev. Biol.

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Erlotinib (ER), as an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has a significant therapeutic effect in lung cancers. However, EGFR TKI resistance inevitably occurs after treatment for approximately 12 months, which weakens its antitumor effect. Here, we identified miR-185-3p as a significantly downregulated microRNA responsible for acquired EGFR TKI resistance in cells and patients with lung cancer. qRT-PCR and Western Blot were performed to determine the relative expression of miR-185-3p in ER-resistant tumor tissues and cells. The viability and apoptosis of lung cancer cells were evaluated by Cell Counting Kit-8 (CCK8) assay and flow cytometry, respectively. The binding between miR-185-3p and liver-type phosphofructokinase (PFKL) was verified by dual luciferase assay. It was found that overexpression of miR-185-3p conferred ER sensitivity in lung cancer cell lines. MiR-185-3p was downregulated in ER-resistant lung cancer cells (H1299/ER and A549/ER). MiR-185-3p inhibited proliferation and induced cell apoptosis in ER-resistant cells. Mechanistically, miR-185-3p downregulation contributed to ER resistance through upregulating the PFKL. Moreover, Mesenchymal to epithelial transition (MET) oncoprotein promoted EGFR-TKI resistance by regulating miR-185-3p and PFKL. These findings revealed a novel mechanism in which downregulation of miR-185-3p may induce overexpression of PFKL and MET and confer ER resistance in lung cells. Combination of PFKL/MET inhibitors and EGFR TKIs could be a rational therapeutic approach for lung cancer patients with EGFR mutation.

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Section: Discussionmentioning

confidence: 99%

Inhibition of miR-185-3p Confers Erlotinib Resistance Through Upregulation of PFKL/MET in Lung Cancers

Zhu

Yuan

2021

Front. Cell Dev. Biol.

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“…The alterations in TGFBR2 expression levels are reported in CRC 22,25 . Small non‐coding RNAs, such as microRNAs (miRNAs) are well known as the post‐transcriptional gene expression regulators in various kinds of cancers, such as CRC 26–30 . For example, miR‐4,319, miR‐143, miR‐20a and miR‐145 are associated with CRC progression 31–34 .…”

Section: Introductionmentioning

confidence: 99%

“…22,25 Small non-coding RNAs, such as microRNAs (miRNAs) are well known as the posttranscriptional gene expression regulators in various kinds of cancers, such as CRC. [26][27][28][29][30] For example, miR-4,319, miR-143, miR-20a and miR-145 are associated with CRC progression. [31][32][33][34] It has been reported that the miR-20a-5p may affect the cellular phosphoinositide 3-kinase-Akt, mitogen-activated protein kinase and TGF-β signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Non‐coding RNAs are correlated to TGF‐β receptor type 2 in patients with colorectal cancer

Abkenar

Mohammadi

Amoli

et al. 2023

The Journal of Gene Medicine

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Background: Multiple molecular expression alterations, particularly in non-coding RNAs, play fundamental roles in the regulations of cellular processes and may relate to the occurrence and progression of colorectal cancer (CRC). In the present study, we investigated the associations between TGFBR2, miR20a-5p and long non-coding RNA (lncRNA) LAMTOR5-AS1 in CRC patients.Methods: Colorectal cancer and adjacent normal tissue samples (n = 34) were prepared from CRC patients. The associations between TGFBR2, miR20a-5p and lncRNA LAMTOR5-AS1 were predicted using bioinformatics tools. The expression levels of TGFBR2, miR20a-5p and lncRNA LAMTOR5-AS1 were measured using a quantitative real-time polymerase chain reaction technique. The TGFBR2 protein values were measured by western blotting. The clinical importance of lncRNA LAMTOR5-AS1 was assessed using receiver operating characteristic curve. Results:The up-regulated levels of TGFBR2 (p = 0.02), TGFBR2 protein (p = 0.008) and lncRNA LAMTOR5-AS1 (p = 0.02) were significantly observed in CRC tissues compared to the adjacent normal tissues. The miR20a-5p expression level (p = 0.009) was downregulated in CRC tissues. In addition, the miR20a-5p expression level was inversely correlated to the TGFBR2 gene (r 2 = 0.88, p < 0.0001), protein (r 2 = 0.95, p < 0.0001) and lncRNA LAMTOR5-AS1 gene (r 2 = 0.93, p < 0.0001) expression levels. Based on the area under curve, the increase of lncRNA LAMTOR5-AS1 expression level with a sensitivity of 64.52% and specificity of 65.52% was considered in CRC patients. Conclusions:We propose that miR20a-5p is inversely related to long non-coding RNA (lncRNA) LAMTOR5-AS, such that it may be involved in the regulation of TGFBR2 expression level in CRC patients.

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“…They have been certified as essential epigenetic factors that regulate gene expression via interacting with the 3’-untranslated region of their downstream target genes, ultimately triggering translation suppression or mRNA degradation 16 . Aberrant miRNA expression is widely observed in NSCLC occurrence and development and contributes to an extensive range of malignant behaviors 17 . Recently, an increasing number of studies have highlighted that the competing endogenous RNA (ceRNA) regulatory network has a role in NSCLC 18–20 .…”

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNA LAMTOR5-AS1 Interference Affects MicroRNA-506-3p/E2F6-Mediated Behavior of Non-Small Cell Lung Cancer Cells

Chen

Wang

et al. 2021

oncol res

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Long noncoding RNA LAMTOR5 antisense RNA 1 (LAMTOR5-AS1) has been certified as a risk predictor and diagnostic biomarker of prostate cancer. However, the expression and exact roles of LAMTOR5-AS1 in non-small cell lung cancer (NSCLC) remain unclear. Thus, we measured LAMTOR5-AS1 expression in NSCLC and gauged its clinical value. The detailed roles and downstream working mechanism of LAMTOR5-AS1 in NSCLC were comprehensively unraveled. qRT-PCR was applied to measure gene expression. Functionally, utilizing small interfering RNA, LAMTOR5-AS1 was ablated, and the functional alterations were addressed by means of different experiments. The targeting activities between LAMTOR5-AS1 and microRNA-506-3p (miR-506-3p) and between miR-506-3p and E2F transcription factor 6 (E2F6) were confirmed by RNA immunoprecipitation and luciferase reporter assays. LAMTOR5-AS1 overexpression in NSCLC was verified in TCGA datasets and our own cohort and manifested an evident relationship with poor prognosis. Interference with LAMTOR5-AS1 led to repression of the proliferation, cloning and metastasis abilities of NSCLC cells in vitro. We further confirmed an obvious increase in LAMTOR5-AS1-silenced NSCLC cell apoptosis. Furthermore, the absence of LAMTOR5-AS1 restricted tumor growth in vivo. Mechanistically, LAMTOR5-AS1 sponged miR-506-3p in NSCLC cells. Furthermore, E2F6, a downstream target of miR-506-3p, was under the control of LAMTOR5-AS1, which was realized by decoying miR-506-3p. Rescue experiments showed that miR-506-3p suppression or E2F6 reintroduction was capable of remitting LAMTOR5-AS1 deficiency-triggered anticarcinogenic actions in NSCLC. Our study confirmed the exact roles of LAMTOR5-AS1 for the first time and revealed that LAMTOR5-AS1 knockdown disrupts the malignancy of NSCLC by targeting the miR-506-3p/E2F6 axis. Targeting the LAMTOR5-AS1/miR-506-3p/E2F6 pathway may be instrumental for managing patients with NSCLC.

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MicroRNAs as Therapeutic Targets for Anticancer Drugs in Lung Cancer Therapy

Cited by 4 publications

References 155 publications

Inhibition of miR-185-3p Confers Erlotinib Resistance Through Upregulation of PFKL/MET in Lung Cancers

Inhibition of miR-185-3p Confers Erlotinib Resistance Through Upregulation of PFKL/MET in Lung Cancers

Non‐coding RNAs are correlated to TGF‐β receptor type 2 in patients with colorectal cancer

Long Noncoding RNA LAMTOR5-AS1 Interference Affects MicroRNA-506-3p/E2F6-Mediated Behavior of Non-Small Cell Lung Cancer Cells

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