MicroRNA-138 functions as a tumor suppressor in osteosarcoma by targeting differentiated embryonic chondrocyte gene 2

Jiang, Baoen; Mu, Weidong; Wang, Jiangquan; Lu, Jianshu; Jiang, Shanyong; Liang, Li; Xu, Haining; Tian, Hongyan

doi:10.1186/s13046-016-0348-5

Cited by 42 publications

(33 citation statements)

References 36 publications

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“…Recent studies have reported that miRNAs regulate endothelial cell apoptosis and senescence-related pro-inflammatory status [7,8]. MiR-138 is an important member of miRNA family and has been shown to be a tumour suppressor in many studies [9,10]. Interestingly, miR-138 was reported to contribute to endothelial cell dysfunction when induced by pro-inflammatory cytokines [3].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of microRNA‐138 alleviates human coronary artery endothelial cell injury and inflammatory response by inhibiting the PI3K/Akt/eNOS pathway

Wang

Yao

et al. 2017

J Cellular Molecular Medi

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This study aimed to investigate the role of miR‐138 in human coronary artery endothelial cell (HCAEC) injury and inflammatory response and the involvement of the PI3K/Akt/eNOS signalling pathway. Oxidized low‐density lipoprotein (OX‐LDL)‐induced HCAEC injury models were established and assigned to blank, miR‐138 mimic, miR‐138 inhibitor, LY294002 (an inhibitor of the PI3K/Akt/eNOS pathway), miR‐138 inhibitor + LY294002 and negative control (NC) groups. qRT‐PCR and Western blotting were performed to detect the miR‐138, PI3K, Akt and eNOS levels and the protein expressions of PI3K, Akt, eNOS, p‐Akt, p‐eNOS, Bcl‐2, Bax and caspase‐3. ELISAs were employed to measure the expressions of TNF‐α, IL‐4, IL‐6, IL‐8, IL‐10 and nitric oxide (NO) and the activities of lactate dehydrogenase (LDH) and eNOS. MTT and flow cytometry were performed to assess the proliferation and apoptosis of HCAECs. Compared to the blank group, PI3K, Akt and eNOS were down‐regulated in the miR‐138 mimic and LY294002 groups but were up‐regulated in the miR‐138 inhibitor group. The miR‐138 mimic and LY294002 groups showed decreased concentrations of TNF‐α, IL‐6, IL‐8 and NO and reduced activities of LDH and eNOS, while opposite trends were observed in the miR‐138 inhibitor group. The concentrations of IL‐4 and IL‐10 increased in the miR‐138 mimic and LY294002 groups but decreased in the miR‐138 inhibitor group. The miR‐138 mimic and LY294002 groups had significantly decreased cell proliferation and increased cell apoptosis compared to the blank group. These findings indicate that up‐regulation of miR‐138 alleviates HCAEC injury and inflammatory response by inhibiting the PI3K/Akt/eNOS signalling pathway.

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Section: Introductionmentioning

confidence: 99%

Overexpression of microRNA‐138 alleviates human coronary artery endothelial cell injury and inflammatory response by inhibiting the PI3K/Akt/eNOS pathway

Wang

Yao

et al. 2017

J Cellular Molecular Medi

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“…In most cases, the tumors have metastasized to the lungs in patients diagnosed with osteosarcomas [4]. Standard neoadjuvant chemotherapy can effectively increase the possibility of limb salvage, which can significantly improve the 5-year survival rate and quality of life in patients with osteosarcomas [5]; however, intrinsic or acquired chemotherapy resistance affects the therapeutic effect [6][7][8]. Previous studies have shown that chemotherapy resistance of tumors is a complex and multistage process, including genes, proteins, miRNAs, and signaling pathways [9,10].…”

Section: Introductionmentioning

confidence: 99%

LncRNA MALAT1 Promotes Cancer Metastasis in Osteosarcoma via Activation of the PI3K-Akt Signaling Pathway

Chen

Huang

Sun

et al. 2018

Cell Physiol Biochem

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Background/Aims: LncRNAs have been reported to be vital regulators of the progression of osteosarcoma, although the underlying mechanisms are not completely understood. Methods: The levels of MALAT1 and miR-129-5p expression were measured using qRT-PCR. Cell growth was determined using the CCK-8 and colony formation assays. Cell migration and invasion were detected using the wound healing and Transwell invasion assays, respectively. Tumor growth was determined with a xenograft model. Results: MALAT1 was significantly up-regulated in osteosarcoma tissues compared with adjacent non-tumor soft tissues. Overexpression of MALAT1 promoted osteosarcoma cell proliferation, migration, and invasion in vitro and enhanced tumor growth in a tumor xenograft mouse model. MALAT1 promoted osteosarcoma progression by modulating stem cell-like properties. Moreover, rescue experiment and luciferase reporter assay results indicated that MALAT1 modulates RET expression by sponging miR-129-5p in osteosarcomas. Furthermore, MALAT1 augmented the expression of downstream proteins of the RET-Akt pathway. MALAT1 was consistently significantly increased in osteosarcoma tissues and MALAT1 expression was positively correlated with tumor size and metastasis. High expression of MALAT1 was significantly associated with poor outcomes in patients with osteosarcomas. MALAT1 expression was positively related to RET and negatively related to miR-129-5p in osteosarcoma samples and xenograft tumors. MALAT1 functioned as an oncogenic lncRNA in osteosarcomas and was as an independent prognostic indicator. Conclusion: Our data revealed for the first time that MALAT1 increases stem cell-like properties by up-regulating RET via sponging miR-129-5p, and thus activates the PI3K-Akt signaling pathway and provides potential therapeutic targets for osteosarcoma treatment.

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“…Beyond the regulatory functions in normal cells, growing evidence has highlighted the important roles of microRNAs in various biological processes of cancers. Among the abundant microRNAs, miR-138 is a member studied extensively and considered as a tumor suppressor in many types of cancers (27,28). In non-small cell lung cancer, overexpression of miR-138 was found to inhibit the proliferation of cancer cells (29).…”

Section: Discussionmentioning

confidence: 99%

α-solanine enhances the chemosensitivity of esophageal cancer cells by inducing microRNA‑138 expression

Wang

et al. 2018

Oncol Rep

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Esophageal cancer is a common malignant tumor worldwide. Inherent and acquired drug resistance are the major challenges faced in anticancer chemotherapy. This study aimed to explore the effects of α-solanine in regards to the chemosensitivity of esophageal cancer cells. We found that α-solanine enhanced the sensitivity of EC9706 and KYSE30 cells to 5-flurouracil (5-FU) and cisplatin (Cis) by promoting drug-induced apoptosis. qRT-PCR and western blotting results showed that α-solanine treatment promoted miR-138 expression and decreased survivin expression in EC9706 and KYSE30 cells. α-solanine also enhanced the inhibitory effects of 5-Fu and Cis in EC9706 transplanted tumors in mouse models. Dual-Luciferase reporter assay results confirmed survivin as the direct target gene of miR-138. MiR-138 inhibited survivin expression in EC9706 and KYSE30 cells. And miR-138 mimic and si-survivin had similar effects with α-solanine in suppressing survivin expression and promoting cancer cell death. miR-138 inhibitor reversed the chemosensitivity-enhancing effect of α-solanine. In EC9706 and KYSE30 cells, survivin overexpression rescued the cancer cells from apoptosis caused by α-solanine and miR-138 mimic expression. From these findings, we conclude that α-solanine enhanced the chemosensitivity of esophageal cancer cells to chemotherapy via the miR-138/survivin pathway. This study provides insight into the molecular mechanism underlying the chemosensitivity-enhancing function of α-solanine and suggests a new chemotherapeutic strategy for esophageal cancer treatment.

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MicroRNA-138 functions as a tumor suppressor in osteosarcoma by targeting differentiated embryonic chondrocyte gene 2

Cited by 42 publications

References 36 publications

Overexpression of microRNA‐138 alleviates human coronary artery endothelial cell injury and inflammatory response by inhibiting the PI3K/Akt/eNOS pathway

Overexpression of microRNA‐138 alleviates human coronary artery endothelial cell injury and inflammatory response by inhibiting the PI3K/Akt/eNOS pathway

LncRNA MALAT1 Promotes Cancer Metastasis in Osteosarcoma via Activation of the PI3K-Akt Signaling Pathway

α-solanine enhances the chemosensitivity of esophageal cancer cells by inducing microRNA‑138 expression

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