The feedback loop between miR-124 and TGF-β pathway plays a significant role in non-small cell lung cancer metastasis

Zu, Lidong; Xue, Yi; Wang, Jinglong; Fu, Yujie; Wang, Xiumin; Xiao, Gang; Hao, Mingang; Sun, Xun; Wang, Yingying; Fu, Guo‐Hui; Wang, Jianhua

doi:10.1093/carcin/bgw011

Cited by 53 publications

(48 citation statements)

References 43 publications

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“…miRNAs can function as oncogenes or tumor suppressor genes in cancer, aiming at restoration of tumor suppressor genes and silence of oncogenes would be a novel anticancer therapy (23). The inhibitory effect of miR-124 in tumor growth and migration, as well as dysregulation of miR-124 has been reported in various tumor types (6)(7)(8)(9). In a previous (13) and the present study, miR-124 was downregulated in GC tissues and cell lines.…”

Section: Discussionsupporting

confidence: 57%

“…Recently, miR-124 has been found down-regulated in multiple tumor types, including cancer (6), prostate (7), lung (8) and colorectal cancer (9). It also been found that miR-124 could inhibit the proliferation of GC cells proliferation by targeting Rho-associated protein kinase 1, enhancer of zeste homolog 2 (EZH2) and sphingosine kinase 1 (SPHK1) (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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Lentivirus-mediated overexpression of miR-124 suppresses growth and invasion by targeting JAG1 and EZH2 in gastric cancer

Chen

et al. 2018

Oncol Lett

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Abstract. expression is downregulated and has a tumor suppressor role in various types of cancer. The present study revealed that genes encoding miR-124 were frequently methylated and the expression of miR-124 was downregulated in gastric cancer tissues. Stable expression of miR-124 using a lentiviral vector inhibited gastric cancer cell growth, migration and invasion in vitro. In addition, overexpression of miR-124 suppressed gastric cancer cell xenograft growth in nude mice. The expression of the Notch ligand Jagged1 (JAG1) and enhancer of zeste homolog 2 (EZH2) was downregulated upon miR-124 overexpression, and silencing of JAG1 or EZH2 by RNA interference also suppressed gastric cancer cell growth, migration and invasion. Furthermore, expression of fibronectin and vimentin, not able elements of the epithelial-mesenchymal transition, were suppressed by overexpression of miR-124 or inhibition of JAG1 or EZH2 expressions in GC. Together, these results indicated that miR-124 suppressed gastric cancer progression, partly through inhibiting JAG1 and EZH2. Thus, lentivirus-mediated overexpression of miR-124 may be a potential therapeutic strategy against gastric cancer.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Lentivirus-mediated overexpression of miR-124 suppresses growth and invasion by targeting JAG1 and EZH2 in gastric cancer

Chen

et al. 2018

Oncol Lett

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“…A strong relationship between miRNA and pathophysiological processes has been reported in the literature [20,21]. As mentioned in the literature review, miR-124 is frequently expressed in multiple tissues to regulate different pathophysiologic processes, for instance, the development of cancer [22][23][24][25][26], as a new therapeutic approach to Parkinson's disease [27], promotes the pathogenesis of Crohn's Disease [28] and contributes to cholangiocyte proliferation in the cholestatic liver [29].…”

Section: Discussionmentioning

confidence: 97%

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

Tang¹,

Yin²,

Liu³

et al. 2017

Cell Physiol Biochem

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Background/Aims: With the aging population increases, senile osteoporosis has become a global public health problem. Previous evidence has shown that miR-124 has important effects on the occurrence and development of osteoporosis. However, the role of miR-124 in the process of osteoclastogenesis is still obscure. Methods: First of all, we measured the expression level of miR-124 in bone marrow monocytes (BMMs) of osteoporotic mice (ovariectomized mice: OVX). Next, we evaluated the alteration of miR-124 during osteoclast differentiation of BMMs. Then, BMMs were transfected with miR-124 mimics or inhibitors to explore the influences of miR-124 on osteoclast differentiation of BMMs in vitro. Furthermore, bioinformatics analysis and luciferase reporter assay were performed for prediction and identification of the target of miR-124. Results: BMMs from OVX mice exhibited lower expression of miR-124 compared with Sham mice. Additionally, miR-124 was down-regulated when BMMs differentiated into osteoclasts. In addition, inhibition of miR-124 promoted BMMs differentiated into osteoclasts in vitro, whereas overexpression of miR-124 attenuated this procedure, demonstrated by increased expression of osteoclast specific genes and TRAP staining. Furthermore, Rab27a was confirmed to be the direct target of miR-124 by bioinformatics, Western blot and luciferase reporter assay analysis. Conclusion: Our findings revealed that miR-124 has an important role in osteoclastogenesis via targeting Rab27a. Thus, targeting miR-124 promises a therapeutic potential in the treatment of osteoporosis.

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“…In lung cancer, high TGF-β serum levels is associated with a poor prognosis, lymph node metastasis, and tumor progression (40,41). In addition, TGF-β was suggested as an independent risk factor for the occurrence of pulmonary metastasis in NSCLC (42). A study also revealed that the presence of p-SMAD2 and 3 was significantly higher in the NSCLC cancer tissues compared with the tumor-free lung tissues (3).…”

Section: Discussionmentioning

confidence: 99%

BAMBI overexpression together with β-sitosterol ameliorates NSCLC via inhibiting autophagy and inactivating TGF-β/Smad2/3 pathway

Wang

et al. 2017

Oncology Reports

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Abstract. Non-small cell lung cancer (NSCLC) has the highest mortality rate among all solid tumors with a poor prognosis. The BMP and activin receptor membrane bound inhibitor (BAMBI) has been identified as a hallmark of NSCLC and β-sitosterol possesses antitumor potentiality. This study explores the effect of BAMBI overexpression and β-sitosterol in the context of NSCLC. The results revealed that the transfection of pcDNA-BAMBI and β-sitosterol treatment significantly reduced the levels of autophagy markers light chain 3 (LC3) II and Beclin 1, whereas the levels of LC3 I and p62 were promoted. The reduced punctate accumulations of GFP-LC3 were detected in pcDNA-BAMBI and β-sitosterol groups, especially in pcDNA-BAMBI + β-sitosterol group. BAMBI overexpression and β-sitosterol induced G0/G1 cell cycle arrest and inhibted cell proliferation in A549 cells. In addition, the levels of transforming growth factor-β (TGF-β)/p-Smad2/3/c-Myc pathway proteins were decreased. The TGF-β overexpression further confirmed that BAMBI overexpression and β-sitosterol treatment suppre ssed autohagy and viability of A549 cells was through TGF-β/Smad2/3/c-Myc pathway. Finally, the tumor growth was suppressed in NSCLC xenografts, and the inhibitory effect was stronger under treatment of pcDNA-BAMBI together with β-sitosterol. These results indicate that BAMBI overexpression and β-sitosterol may serve as novel targets for the treatment of NSCLC. IntroductionLung cancer is the leading cause of deaths with the most rapidly increasing incidence worldwide. Non-small cell lung cancer (NSCLC) has the highest mortality rate among all solid tumors with a poor prognosis (1). More than half of lung carcinomas are detected in a progressed or already metastasized state with a 5-year survival, for lacking of characteristic early symptoms (2). The general therapy treating the majority of patients is chemotherapy, which often induces resistance (3). It is necessary to develop novel therapeutic approaches to better understand the lung cancer progression.Autophagy is a fundamental cellular homeostatic process that cells use to degrade and recycle cellular proteins (4). This process can be induced in response to either intracellular or extracellular factors, such as hypoxia, low cellular energy state and organelle damage (5). The microtubule-associated protein 1 light chain 3 (LC3), functions as a structural component in the formation of autophagosomes. The conversion of the cytosolic form of LC3 (LC3 I) to lipidated form (LC3 II) indicates autophagosome formation (6). Beclin 1, is required for the initiation and in the process of autophagosome formation (7). p62 acts as a receptor or adaptor for autophagic degradation of ubiquitinated proteins, the upregulation of p62 is commonly detected in human tumors and contributes dire ctly to tumorigenesis (8). Thus, LC3, Beclin 1 and p62 were considered as autophagy markers in many studies (9,10).Transforming growth factor-β (TGF-β) has a crucial role in homeostasis, fibrosis angiogenesis, carcinogenesis and d...

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The feedback loop between miR-124 and TGF-β pathway plays a significant role in non-small cell lung cancer metastasis

Cited by 53 publications

References 43 publications

Lentivirus-mediated overexpression of miR-124 suppresses growth and invasion by targeting JAG1 and EZH2 in gastric cancer

Lentivirus-mediated overexpression of miR-124 suppresses growth and invasion by targeting JAG1 and EZH2 in gastric cancer

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

BAMBI overexpression together with β-sitosterol ameliorates NSCLC via inhibiting autophagy and inactivating TGF-β/Smad2/3 pathway

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