miR‑142‑5p suppresses proliferation and promotes apoptosis of human osteosarcoma cell line, HOS, by targeting PLA2G16 through the ERK1/2 signaling pathway

Cheng, Deliang; Li, Jiageng; Zhang, Lijun; Hu, Leiming

doi:10.3892/ol.2018.9712

Cited by 20 publications

(22 citation statements)

References 38 publications

(39 reference statements)

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“…Then, we chose miR-142-5p for our further study. miR-142-5p, identified as a tumor suppressor gene, is proved to be attenuated in various cancers such as osteosarcoma, ovarian cancer, gastric cancer, and NSCLC [29][30][31][32] . In the present study, we found that TTN-AS1 shared a complementary binding site with miR-142-5p, thus TTN-AS1 could bind to miR-142-5p and decrease its expression in LUAD cells.…”

Section: Discussionmentioning

confidence: 99%

LncRNA TTN-AS1 promotes migration, invasion, and epithelial mesenchymal transition of lung adenocarcinoma via sponging miR-142-5p to regulate CDK5

et al. 2019

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Emerging evidence suggests that long noncoding RNA (lncRNA) plays pivotal roles in regulating various biological process in human cancers. Titin-antisense RNA1 (TTN-AS1) has been regarded as a tumor promoting lncRNA in numerous cancers. However, the clinical significance and biological function of TTN-AS1 in lung adenocarcinoma (LUAD) remain unclear. In the present study, we revealed that the expression of TTN-AS1 was upregulated in LUAD tissues and cell lines. High TTN-AS1 expression was associated with TNM stage and lymph node metastasis of LUAD patients. In addition, high expression of TTN-AS1 was correlated with poor postoperative prognosis of LUAD patients. Knockdown of TTN-AS1 significantly inhibited the growth, proliferation, migration, and invasion ability of LUAD cells in vitro. Then, by using bioinformation analysis and luciferase reporter experiment, we identified that TTN-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-142-5p to regulate the expression of cyclindependent kinase 5 (CDK5) in LUAD. Since CDK5 is a key regulator in the process of epithelial mesenchymal transition (EMT), we detected the expression of EMT-related proteins, consequently, EMT was suppressed by knockdown of TTN-AS1 while this phenomenon was rescued by miR-142-5p inhibitor. Taken above, our study revealed that TTN-AS1 played an important role in LUAD progression. TTN-AS1/miR-142-5p/CDK5 regulatory axis may serve as a novel therapeutic target in the treatment of LUAD.

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Section: Discussionmentioning

confidence: 99%

LncRNA TTN-AS1 promotes migration, invasion, and epithelial mesenchymal transition of lung adenocarcinoma via sponging miR-142-5p to regulate CDK5

et al. 2019

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“…Notably, this negative effect of SFN was maintained in the S. aureus-infected Nrf2 -/-BMdM. The expression levels of miR-142-5p and miR-146a-5p have been associated with cell apoptosis (26,27). Therefore, the effects of SFN on the levels of these miRNAs were examined.…”

Section: Sfn Affects Intracellular S Aureus Survival and Cell Apoptosismentioning

confidence: 99%

Sulforaphane reduces intracellular survival of Staphylococcus aureus in macrophages through inhibition of JNK and p38 MAPK‑induced inflammation

Deramaudt¹,

Ali²,

Vinit³

et al. 2020

Int J Mol Med

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Macrophages are active contributors to the innate immune defense system. As macrophage activation is clearly affected by the surrounding microenvironment, the present study investigated the effect of sulforaphane (SFN) on the bactericidal activity of macrophages and the underlying molecular mechanisms involved in this process. Human THP-1-derived macrophages, primary human peripheral blood mononuclear cell-derived macrophages, and primary mouse bone marrow derived-macrophages (BMdMs) pretreated with SFN or dMSO were utilized in a model of Staphylococcus aureus infection. The results suggested that SFN pretreatment of macrophages effectively repressed the intracellular survival of S. aureus through modulation of p38/JNK signaling and decreased S. aureus-induced caspases-3/7-dependent cell apoptosis, potentially through downregulation of microRNA (miR)-142-5p and miR-146a-5p. As SFN is a well-known activator of nuclear factor erythroid 2-related factor 2 (Nrf2), Nrf2 -/-BMdMs were used to demonstrate that the SFN-mediated inhibitory effect was independent of Nrf2. Nevertheless, an increase in intracellular bacterial survival in Nrf2-deficient macrophages was observed. In addition, SFN pretreatment suppressed S. aureus-induced transcriptional expression of genes coding for the proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), as well as for the M1 markers c-c motif chemokine receptor 7, IL-23 and inducible nitric oxide synthase (iNOS). Western blot analysis indicated that S. aureus challenge activated p38 mitogen-activated protein kinase (MAPK) (p38) and c-Jun N-terminal kinase (JNK) MAPK signaling pathways, while SFN pretreatment prevented p38 and JNK phosphorylation. Pretreatment with 2 specific inhibitors of p38 and JNK, SB203580 and SP600125, respectively, resulted in a decrease in S. aureus-induced proinflammatory gene expression levels compared with those observed in the SFN-pretreated macrophages. Furthermore, THP-1-derived macrophages pretreated with SB203580 or SP600125 prior to bacterial infection exhibited a significant inhibition in intracellular S. aureus survival.In conclusion, we hypothesize that concomitant targeting of the p38/JNK-inflammatory response and the S. aureus-induced apoptosis with SFN may be a promising therapeutic approach in S. aureus infection.

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“…Second, miR-142-5p has been demonstrated to serve as a tumor suppressor in different cancer types. For instance, a higher level of miR-142-5p-induced apoptosis was found in osteosarcoma via suppression of Erk-associated signaling [38]. In another example, miR-142-5p targeted several antiapoptotic genes, including baculoviral IAP repeat-containing 3 (BIRC3), B-cell lymphoma-2 (BCL2), BCL2-like 2 (BCL2L2), and myeloid cell leukemia sequence 1 (MCL1), and could improve cisplatin-mediated anticancer function in ovarian cancer [39].…”

Section: Discussionmentioning

confidence: 99%

Disruption of Cancer Metabolic SREBP1/miR-142-5p Suppresses Epithelial–Mesenchymal Transition and Stemness in Esophageal Carcinoma

Huang

Hsu

et al. 2019

Cells

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Elevated activity of sterol regulatory element-binding protein 1 (SREBP1) has been implicated in the tumorigenesis of different cancer types. However, the functional roles of SREBP1 in esophageal cancer are not well appreciated. Here, we aimed to investigate the therapeutic potential of SREBP1 and associated signaling in esophageal cancer. Our initial bioinformatics analyses showed that SREBP1 expression was overexpressed in esophageal tumors and correlated with a significantly lower overall survival rate in patients. Additionally, tumor suppressor miR-142-5p was predicted to target SREBP1/ZEB1 and a lower miR-142-5p was correlated with poor prognosis. We then performed in vitro experiments and showed that overexpressing SREBP1 in OE33 cell line led to increased abilities of colony formation, migration, and invasion; the opposite was observed in SREBP1-silenced OE21cells and SREBP1-silencing was accompanied by the reduced mesenchymal markers, including vimentin (Vim) and ZEB1, while E-cadherin and tumor suppressor miR-142-5p were increased. Subsequently, we first demonstrated that both SREBP1 and ZEB1 were potential targets of miR-142-5p, followed by the examination of the regulatory circuit of miR-142-5p and SREBP1/ZEB1. We observed that increased miR-142-5p level led to the reduced tumorigenic properties, such as migration and tumor sphere formation, and both observations were accompanied by the reduction of ZEB1 and SREBP1, and increase of E-cadherin. We then explored the potential therapeutic agent targeting SREBP1-associated signaling by testing fatostatin (4-hydroxytamoxifen, an active metabolite of tamoxifen). We found that fatostatin suppressed the cell viability of OE21 and OE33 cells and tumor spheres. Interestingly, fatostatin treatment reduced CD133+ population in both OE21 and OE33 cells in concert of increased miR-142-5p level. Finally, we evaluated the efficacy of fatostatin using a xenograft mouse model. Mice treated with fatostatin showed a significantly lower tumor burden and better survival rate as compared to their control counterparts. The treatment of fatostatin resulted in the reduced staining of SREBP1, ZEB1, and Vim, while E-cadherin and miR-142-5p were increased. In summary, we showed that increased SREBP1 and reduced miR-142-5p were associated with increased tumorigenic properties of esophageal cancer cells and poor prognosis. Cells 2020, 9, 7 2 of 15Preclinical tests showed that suppression of SREBP1 using fatostatin led to the reduced malignant phenotype of esophageal cancer via the reduction of EMT markers and increased tumor suppressor, miR-142-5p. Further investigation is warranted for the clinical use of fatostatin for the treatment of esophageal malignancy.

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miR‑142‑5p suppresses proliferation and promotes apoptosis of human osteosarcoma cell line, HOS, by targeting PLA2G16 through the ERK1/2 signaling pathway

Cited by 20 publications

References 38 publications

LncRNA TTN-AS1 promotes migration, invasion, and epithelial mesenchymal transition of lung adenocarcinoma via sponging miR-142-5p to regulate CDK5

LncRNA TTN-AS1 promotes migration, invasion, and epithelial mesenchymal transition of lung adenocarcinoma via sponging miR-142-5p to regulate CDK5

Sulforaphane reduces intracellular survival of Staphylococcus aureus in macrophages through inhibition of JNK and p38 MAPK‑induced inflammation

Disruption of Cancer Metabolic SREBP1/miR-142-5p Suppresses Epithelial–Mesenchymal Transition and Stemness in Esophageal Carcinoma

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