Tumor Necrosis Factor-Induced miR-146a Upregulation Promotes Human Lung Adenocarcinoma Metastasis by Targeting Merlin

Sánchez, Nilda; Medrano-Jiménez, Elisa; Aguilar‐León, Diana; Pérez-Martı́nez, Leonor; Pedraza‐Alva, Gustavo

doi:10.1089/dna.2019.4620

Cited by 7 publications

(4 citation statements)

References 48 publications

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“…Alcantara and Garcia (34) revealed that downregulation of NF2 promoted the migration and proliferation of lung cancer cells. Sánchez et al (35) also reported that invasive and metastatic lung adenocarcinoma exhibited lower Merlin protein levels compared with noninvasive tumors, and suggested that Merlin could be a promising therapeutic target to inhibit the progression of lung adenocarcinoma. Therefore, it may be hypothesized that Merlin has a cancer suppressive role in NSCLC, whereas INHBA may abrogate the cancer-suppressing effect of Merlin, and promote the invasion and metastasis of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non‑small cell lung cancer

Zhang

Yan

et al. 2021

Mol Med Rep

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Inhibin βA (INHBA) serves a prognostic and tumor-promoting role in numerous types of cancer. The present study aimed to determine the clinical significance of INHBA in non-small cell lung cancer (NSCLC) and the mechanisms underlying its potential tumor-promoting effect. INHBA expression was detected in clinical NSCLC samples using immunohistochemistry. In vivo loss-and gain-of-function studies were performed to determine the effects of INHBA on NSCLC invasion. In addition, protein and mRNA expression levels of INHBA, yes-associated protein (YAP), large tumor suppressor 1/2 kinase (LATS1/2), connective tissue growth factor, cysteine rich angiogenic inducer 61 and Merlin were assessed using western blotting and reverse transcription-quantitative PCR, respectively, to investigate the mechanism by which INHBA may affect the invasion of NSCLC. The present study revealed that INHBA was significantly upregulated in 238 clinical NSCLC samples compared with its expression levels in paired adjacent non-cancerous tissues, and in metastatic nodules compared with in primary tumors. Notably, high INHBA expression was statistically associated with clinicopathological features, including poor differentiation and advanced tumor stage. INHBA positivity was statistically related to decreased 5-year overall survival, for which INHBA was an independent prognostic factor. Furthermore, INHBA promoted NSCLC invasion in vitro. In NSCLC, INHBA expression was associated with the nuclear levels of YAP and INHBA overexpression enhanced the invasive abilities of NSCLC cells via inhibiting the Hippo pathway. Mechanistically, INHBA inhibited l LATS1/2 phosphorylation and induced YAP nuclear translocation by downregulating the protein expression levels of Merlin. In conclusion, INHBA may negatively regulate the Hippo pathway to act as a tumor promotor, and could represent a marker of prognosis in NSCLC.

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Section: Discussionmentioning

confidence: 99%

Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non‑small cell lung cancer

Zhang

Yan

et al. 2021

Mol Med Rep

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“…Previous studies have identified many genes that are important for DNA repair and that have tumor suppressor activity, and which are targeted directly by mir146a. These genes include DDIT3 (DNA damage-inducible transcript 3) [34], FANCM (Fanconi anemia, complementation group M) [35], Merlin tumor suppressor [36,37], NME1 (NME/NM23 nucleoside diphosphate kinase 1) [38], SMAD4 [39,40]. FLAP (5-Lipoxygenase Activating Protein) [41], HTT (Huntingtin) [42], CADM2 (cell adhesion molecule 2) [43], IRAK1 (interleukin 1 receptor associated kinase 1), TRAF6 (tumor necrosis factor receptor-associated factor-6), and NUMB (NUMB Endocytic Adaptor Protein) [44].…”

Section: Discussionmentioning

confidence: 99%

Impacts of Mir146a Genotypes on Bladder Cancer Risk in Taiwan

Wang,

Chang,

Liao

et al. 2023

Biomedicines

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The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in mir146a and mir196a and bladder cancer (BLCA) risk in Taiwan. The genotypes of mir146a rs2910164 and mir196a rs11614913 were determined in 375 BLCA patients and 375 healthy controls using PCR-RFLP methodology, and their associations with BLCA risk were evaluated. The study also measured the serum expression level of mir146a using quantitative RT-PCR. The results showed that the distributions of CC, CG and GG genotypes of mir146a rs2910164 were 31.7%, 45.6% and 22.7% in the control group, and 21.9%, 44.3% and 33.8% in the case group, respectively. In logistic regression analyses, the heterozygous variant genotype CG carriers showed a marginally significant association with increased BLCA risk (OR = 1.41, 95% CI = 0.99–2.01), while the homozygous variant genotype GG carriers had a 2.17-fold increased risk of BLCA (OR = 2.17, 95%CI = 1.46–3.21). Moreover, carriers of the GG/CG genotypes had significantly higher serum levels of mir146a than those with the CC genotype (p < 0.0001), indicating a genotype–phenotype correlation. In contrast, mir196a rs11614913 was not associated with BLCA risk. Therefore, the genotypes of mir146a rs2910164 may serve as a useful biomarker for predicting the risk of BLCA.

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“…Many studies found that miR-146a promoted cisplatin sensitivity or reduced cisplatin resistance and thus regressed metastasis in lung cancer via certain molecular targets already discussed in the manuscript. However, a recent study found that miR-146a significantly overexpressed, along with a reduced expression of tumor suppressor Merlin protein, and experimentally proved its direct target in lung adenocarcinoma [86] (Figure 3). lated miR-146a/146b expression, which in turn negatively regulated IL-1α induced cytokine secretion.…”

Section: Mir-146a As a Metastatic Modulatormentioning

confidence: 97%

Clinico-Pathological Importance of miR-146a in Lung Cancer

et al. 2021

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Lung cancer is a well-known malignant tumor of the respiratory tract, which has caused a significant level of damage to human health in the 21st century. Micro-RNAs (miRNAs) are tiny, non-coding RNA stem-loop structures with a length of roughly 20–25 nucleotides that function as powerful modulators of mRNA and protein products of a gene. miRNAs may modulate many biological processes involving growth, differentiation, proliferation, and cell death and play a key role in the pathogenesis of various types of malignancies. Several accumulating pieces of evidence have proven that miRNA, especially miR-146a, are crucial modulators of innate immune response sequences. A novel and exciting cancer research field has involved miRNA for the detection and suppression of cancer. However, the actual mechanism which is adopted by these miRNA is still unclear. miRNAs have been used as a cancer-associated biomarker in several studies, suggesting their altered expression in various cancers compared to the normal cells. The amount of expression of miRNA can also be used to determine the stage of the disease, aiding in early detection. In breast, pancreatic, and hepatocellular carcinoma, and gastric cancer, cancer cell proliferation and metastasis has been suppressed by miR-146a. Changes in miR-146a expression levels have biomarker importance and possess a high potential as a therapeutic target in lung cancer. It retards epithelial-mesenchymal transition and promotes the therapeutic action of anticancer agents in lung cancer. Studies have also suggested that miR-146a affects gene expression through different signaling pathways viz. TNF-α, NF-κB and MEK-1/2, and JNK-1/2. Further research is required for understanding the molecular mechanisms of miR-146a in lung cancer. The potential role of miR-146a as a diagnostic marker of lung cancer must also be analyzed. This review summarizes the tumor-suppressing, anti-inflammatory, and antichemoresistive nature of miR-146a in lung cancer.

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Tumor Necrosis Factor-Induced miR-146a Upregulation Promotes Human Lung Adenocarcinoma Metastasis by Targeting Merlin

Cited by 7 publications

References 48 publications

Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non‑small cell lung cancer

Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non‑small cell lung cancer

Impacts of Mir146a Genotypes on Bladder Cancer Risk in Taiwan

Clinico-Pathological Importance of miR-146a in Lung Cancer

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