Downregulation of miR‑136 promotes the progression of osteosarcoma and is associated with the prognosis of patients with osteosarcoma

Chu, Yan-chen; Hu, Xiaoli; Wang, Guangfeng; Wang, Zhijie; Wang, Yanjin

doi:10.3892/ol.2019.10203

Cited by 13 publications

(10 citation statements)

References 42 publications

(37 reference statements)

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“…In osteosarcoma, several miRNAs have already been demonstrated to crucially regulate proliferation, migration, invasion, and apoptosis [13][14][15][16]. In addition, miRNAs have been identified that act as tumor suppressors and might serve as prognostic markers for osteosarcoma [17,18]. Further, miRNAs have been shown to be involved in the development of chemoresistance [19,20] and to be suitable as biomarkers for the early diagnosis of osteosarcoma [21,22].…”

Section: Of 14mentioning

confidence: 99%

Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

Fellenberg

Lehner

Saehr

et al. 2019

Cancers

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Since the introduction of high-dose chemotherapy about 35 years ago, survival rates of osteosarcoma patients have not been significantly improved. New therapeutic strategies replacing or complementing conventional chemotherapy are therefore urgently required. MicroRNAs represent promising targets for such new therapies, as they are involved in the pathology of multiple types of cancer, and aberrant expression of several miRNAs has already been shown in osteosarcoma. In this study, we identified silencing of miR-127-3p and miR-376a-3p in osteosarcoma cell lines and tissues and investigated their role as potential tumor suppressors in vitro and in vivo. Transfection of osteosarcoma cells (n = 6) with miR-127-3p and miR-376a-3p mimics significantly inhibited proliferation and reduced the colony formation capacity of these cells. In contrast, we could not detect any influence of miRNA restoration on cell cycle and apoptosis induction. The effects of candidate miRNA restoration on tumor engraftment and growth in vivo were analyzed using a chicken chorioallantoic membrane (CAM) assay. Cells transfected with mir-127-3p and miR-376a-3p showed reduced tumor take rates and tumor volumes and a significant decrease of the cumulative tumor volumes to 41% and 54% compared to wildtype cells. The observed tumor suppressor function of both analyzed miRNAs indicates these miRNAs as potentially valuable targets for the development of new therapeutic strategies for the treatment of osteosarcoma.

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Section: Of 14mentioning

confidence: 99%

Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

Fellenberg

Lehner

Saehr

et al. 2019

Cancers

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“…As intrinsic regulators, miRNAs have been shown to play critical roles in chondrocyte proliferation, differentiation, and endochondral ossification 16‐19 . In addition, aberrant miRNA expression is involved in many bone‐related disorders, including osteoarthritis, osteoporosis, and bone tumors 20‐22 . To the best of our knowledge, the role of miRNAs in the endochondral ossification of the acetabular roof has not yet been analyzed in the DDH setting.…”

Section: Introductionmentioning

confidence: 99%

Chondrocyte suppression is mediated by miR‐129‐5p via GDF11/SMAD3 signaling in developmental dysplasia of the hip

Liu

Deng

Ding

et al. 2020

Journal Orthopaedic Research

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Recent studies have shown that developmental dysplasia of the hip (DDH) during childhood and in animal models is associated with impaired endochondral ossification of the roof of the acetabulum, yet the molecular mechanism of this pathology remains unknown. To address this, an animal model of DDH was established in 4‐week‐old New Zealand white rabbits by cast immobilization of knee extension. Fifty‐six rabbits of DDH were involved in this study, including 21 male rabbits and 25 female rabbits. High‐throughput RNA sequencing identified 18 differentially expressed microRNAs; miR‐129‐5p downregulation was further confirmed by quantitative polymerase chain reaction. Bioinformatics and luciferase reporter assay identified growth differentiation factor 11 (GDF11) as the target gene of miR‐129‐5p in vitro. miR‐129‐5p downregulation increased GDF11 expression, which induced the phosphorylation of SMAD family member 3. As a result, the expression of runt‐related transcription factor 2, Indian hedgehog homolog, and collagen type X was inhibited in vitro. Meanwhile, Alizarin Red S and Von Kossa staining revealed reduced formation of mineralized nodules by chondrocytes after miR‐129‐5P downregulation compared with the control. Additionally, proliferation assays and flow cytometry confirmed the suppression of chondrocyte proliferation and G1 cell cycle arrest following miR‐129‐5p downregulation. These findings indicate that miR‐129‐5p is able to suppress chondrocyte proliferation and hypertrophic differentiation and decrease mineralization via the miR‐129‐5p/GDF11/SMAD3 axis. This could present the underlying cause for the observed DDH‐associated ossification impairment of the acetabular roof.

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“…Of note, the expression of miR-136 was significantly upregulated in trophoblast cells treated with high-glucose stimulation. Previous studies have reported the regulatory effect of miR-136 on cell proliferation in different kinds of cell, such as keratinocytes [ 35 ] and osteosarcoma cells [ 36 ]. Nevertheless, whether miR-136 could influence trophoblast cell proliferation remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of miR-136 in Gestational Diabetes Mellitus Mediates the High-Glucose-Induced Trophoblast Cell Injury through Targeting E2F1

Zhang

Wang

Chen

et al. 2020

International Journal of Genomics

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Background. Gestational diabetes mellitus (GDM) seriously affects the health of mothers and infants. The high-glucose-induced inhibition in trophoblast cell viability is an important event in GDM pathogenesis. This study evaluated the expression and clinical significance of miR-136 in GDM patients, and the biological function and related mechanisms of miR-136 in the regulation of trophoblast cell proliferation were explored. Methods. The expression of miR-136 in serum and placenta of GDM patients was measured using quantitative Real-Time PCR. Trophoblast cells were stimulated with high-glucose medium to mimic the pathological changes of GDM, and the effect of miR-136 was examined by CCK-8 assay. A luciferase reporter assay was used to confirm the target gene of miR-136, and the relationship of E2F transcription factor 1 (E2F1) with miR-136 in GDM was further analyzed. Results. miR-136 expression was significantly elevated in GDM serum and tissue samples. By high-glucose treatment, trophoblast cell proliferation was inhibited and miR-136 expression was promoted. The knockdown of miR-136 could promote the proliferation of trophoblast cells exposed to high glucose, whereas the overexpression of miR-136 could suppress it. In addition, E2F1 was identified as a target gene of miR-136, which could mediate the regulatory effect of miR-136 on trophoblast cell proliferation. Conclusion. Collectively, miR-136 expression is increased in both serum and placental tissues in GDM patients, and miR-136 mediates the inhibiting effect of high glucose on trophoblast cell viability by targeting E2F1.

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Downregulation of miR‑136 promotes the progression of osteosarcoma and is associated with the prognosis of patients with osteosarcoma

Cited by 13 publications

References 42 publications

Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

Chondrocyte suppression is mediated by miR‐129‐5p via GDF11/SMAD3 signaling in developmental dysplasia of the hip

Differential Expression of miR-136 in Gestational Diabetes Mellitus Mediates the High-Glucose-Induced Trophoblast Cell Injury through Targeting E2F1

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