miR-708-5p enhances erlotinib/paclitaxel efficacy and overcomes chemoresistance in lung cancer cells

Monteleone, Nicholas J.; Lutz, Carol S.

doi:10.18632/oncotarget.27840

Cited by 15 publications

(13 citation statements)

References 70 publications

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“…However, others found that miR-708-5p was decreased in metastatic lung cancer tissues and cells [ 28 , 99 ]. Additionally, Monteleone et al observed that miR-708-5p enhanced the effectiveness of erlotinib and paclitaxel [ 100 ].…”

Section: Resultsmentioning

confidence: 99%

The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

Szczyrek

Bitkowska

Jutrzenka

et al. 2022

JPM

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Lung cancer remains a leading cause of cancer-related deaths worldwide, overtaking colon, breast, and prostate cancer-related deaths. Due to the limited diagnostic possibilities, it is often diagnosed after it has reached an advanced stage. The delayed diagnosis significantly worsens the patient’s prognosis. In recent years, we have observed an increased interest in the use of microRNAs (miRNAs) as diagnostic, predictive, and prognostic markers in non-small-cell lung cancer (NSCLC). The abnormal expression levels of the miRNAs could be used to detect NSCLC in its early stages while it is still asymptomatic. This could drastically improve the clinical outcome. Furthermore, some miRNAs could serve as promising predictive and prognostic factors for NSCLC. Some of the currently available studies have shown a correlation between the miRNAs’ levels and the sensitivity of tumour cells to different treatment regimens. Analysing and modulating the miRNAs’ expression could be a way to predict and improve the treatment’s outcome.

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Section: Resultsmentioning

confidence: 99%

The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

Szczyrek

Bitkowska

Jutrzenka

et al. 2022

JPM

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“…Previously, we investigated the role of miRNAs miR-708-5p and miR-146a in the regulation of AA signaling. We demonstrated that dysregulation of miR-708-5p and miR-146a leads to significantly increased production of PGE 2 in lung cancer cells [ 28 , 31 , 58 ]. COX-2 protein degradation is mediated by multiple pathways, providing additional post-translational mechanisms regulating COX-2-derived PGE 2 production [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

PACER lncRNA regulates COX-2 expression in lung cancer cells

Desind

Iacona

et al. 2022

Oncotarget

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Long noncoding RNAs (lncRNAs) are known to regulate gene expression; however, in many cases, the mechanism of this regulation is unknown. One novel lncRNA relevant to inflammation and arachidonic acid (AA) metabolism is the p50-associated COX-2 extragenic RNA (PACER). We focused our research on the regulation of PACER in lung cancer. While the function of PACER is not entirely understood, PACER is known to play a role in inflammation-associated conditions. Our data suggest that PACER is critically involved in COX-2 transcription and dysregulation in lung cancer cells. Our analysis of The Cancer Genome Atlas (TCGA) expression data revealed that PACER expression is significantly higher in lung adenocarcinomas than normal lung tissues. Additionally, we discovered that elevated PACER expression strongly correlates with COX-2 expression in lung adenocarcinoma patients. Specific siRNA-mediated knockdown of PACER decreases COX-2 expression indicating a direct relationship. Additionally, we show that PACER expression is induced upon treatment with proinflammatory cytokines to mimic inflammation. Treatment with prostaglandin E2 (PGE 2 ) induces both PACER and COX-2 expression, suggesting a PGE 2 -mediated feedback loop. Inhibition of COX-2 with celecoxib decreased PACER expression, confirming this self-regulatory process. Significant overlap between the COX-2 promotor and the PACER promotor led us to investigate their transcriptional regulatory mechanisms. Treatment with pharmacologic inhibitors of NF-κB or AP-1 showed a modest effect on both PACER and COX-2 expression but did not eliminate expression. These data suggest that the regulation of expression of both PACER and COX-2 is complex and intricately linked.

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“…MiR-708 may also regulate immune evasion, by directly targeting CD47 (a transmembrane protein that inhibits phagocytosis in T cell acute lymphoblastic leukemia) and other important immunoregulatory proteins such as B7-H3 [ 41 ], KPNA4 [ 42 ], and CD38 [ 43 ]. Furthermore, miR-708 regulation of quiescence and self-renewal targeting of the focal-adhesion associated protein Tensin3 [ 44 ], further inhibits cancer metastasis and overcomes the chemoresistance [ 45 , 46 ].…”

Section: Mir-708 Overviewmentioning

confidence: 99%

The Double Face of miR-708: A Pan-Cancer Player with Dissociative Identity Disorder

Oliveira

Mathias

Oliveira

et al. 2022

Genes

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Over the last decades, accumulating evidence has shown tumor-dependent profiles of miR-708, being either up- or downregulated, and thus, acting as a “Janus” regulator of oncogenic pathways. Herein, its functional duality was assessed through a thorough review of the literature and further validation in silico using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In the literature, miR-708 was found with an oncogenic role in eight tumor types, while a suppressor tumor role was described in seven cancers. This double profile was also found in TCGA and GEO databases, with some tumor types having a high expression of miR-708 and others with low expression compared with non-tumor counterparts. The investigation of validated targets using miRBase, miRTarBase, and miRecords platforms, identified a total of 572 genes that appeared enriched for PI3K-Akt signaling, followed by cell cycle control, p53, Apellin and Hippo signaling, endocrine resistance, focal adhesion, and cell senescence regulations, which are all recognized contributors of tumoral phenotypes. Among these targets, a set of 15 genes shared by at least two platforms was identified, most of which have important roles in cancer cells that influence either tumor suppression or progression. In a clinical scenario, miR-708 has shown to be a good diagnostic and prognosis marker. However, its multitarget nature and opposing roles in diverse human tumors, aligned with insufficient experimental data and the lack of proper delivery strategies, hamper its potential as a sequence-directed therapeutic.

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miR-708-5p enhances erlotinib/paclitaxel efficacy and overcomes chemoresistance in lung cancer cells

Cited by 15 publications

References 70 publications

The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

PACER lncRNA regulates COX-2 expression in lung cancer cells

The Double Face of miR-708: A Pan-Cancer Player with Dissociative Identity Disorder

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