RESUMO
Increasing reports suggest that discovery of microRNAs (miRNAs) might provide a novel therapeutical target for human cancers, including osteosarcoma. Previous studies have shown that miR-32 was dysregulated in breast and endometrial cancer. However, its biological roles in osteosarcoma remain unclear. In the current study, we found that miR-32 was significantly down-regulated in osteosarcoma tissues, compared with the adjacent normal tissues. In vitro studies further demonstrated that miR-32 mimics were able to suppress, while its antisense oligos promoted cell proliferation in Saos-2 and U2OS cells. At the molecular level, our data further revealed that expression of Sox9 was negatively regulated by miR-32. Therefore, our results identify an important role for miR-32 in the osteosarcoma through regulating Sox9 expression.
Assuntos
Neoplasias Ósseas/patologia , MicroRNAs/metabolismo , Osteossarcoma/patologia , Fatores de Transcrição SOX9/metabolismo , Western Blotting , Neoplasias Ósseas/metabolismo , Proliferação de Células , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Invasividade Neoplásica/fisiopatologia , Osteossarcoma/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Menin, encoded by MEN1 gene, has been viewed as a tumor suppressor in several types of tumors, such as insulinoma, parathyroid tumor, and adrenocortical and lung carcinoma. However, its expression and molecular regulation mechanism in osteosarcoma has not been elucidated. Here, our results show menin expression is significantly down-regulated in osteosarcoma tissues, compared with adjacent normal tissues. Besides, we report that MicroRNA-142-3p as a novel target of menin. Up-regulation of MicroRNA-142-3p by menin overexpression inhibits cell proliferation in U2OS and MG63 cells. At the molecular level, MicroRNA-142-3p inhibits the protein expression of FASN through binding to its 3'-untranslated region. Therefore, we elucidate a novel regulation pathway in osteosarcoma cells and suggest a potential therapeutic approach for the tumor therapy.
Assuntos
Neoplasias Ósseas/genética , Proliferação de Células , Ácido Graxo Sintase Tipo I/genética , MicroRNAs/genética , Osteossarcoma/genética , Proteínas Proto-Oncogênicas/genética , Western Blotting , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Regulação para Baixo , Ácido Graxo Sintase Tipo I/biossíntese , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor , Humanos , MicroRNAs/metabolismo , Osteossarcoma/patologia , Proteínas Proto-Oncogênicas/metabolismo , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
OBJECTIVE: To observe the different efficacies of intradiscal interventional therapy for patients with degenerative chronic discogenic low back pain and end-plate Modic changes through different types of injection and to evaluate the potential therapeutic value of intradiscal injection treatment for degenerative chronic discogenic low back pain with different types of end-plate Modic changes by using appropriate injection. METHODS: Patients with single segmental degenerative chronic discogenic low back pain proved by discography were classified as Modic type I predominant change (including Modic Type I & Modic type I predominant mixed Type I/II) and Modic type II predominant change (including Modic Type II & Modic Type II predominant mixed Type II/I) according to the end-plate Modic changes on MRI. All received the intradiscal injection treatment. Patients were divided into three groups: (1) A group (control group): intradiscal injection of normal saline 3 ml; (2) B group (treatment group): intradiscal injection of diprospan (compound betamethasone) 3 ml; (3) C group (treatment group): interventional injection of diprospan (compound betamethasone) 1 ml + songmeile (cervus & cucumis polypeptide injection) 2 ml. Pain and function were evaluated by pain visual analogue scale (VAS) and Oswestry disability index (ODI). T-test was applied for efficacy comparison in each group at pre-operation, 3 months and 6 months post-operation. RESULTS: Sixty patients were included. There were 39 males and 21 females with a mean age of 41.6 years old (26 - 58). There were 10 patients in each group: A-Modic I, A-Modic II; B-Modic I, B-Modic II; C-Modic I, C-Modic II. There was no significant statistical difference in preoperative VAS and Oswestry scores among groups; VAS and Oswestry scores of B group and C group at 3 months and 6 months post-operation were significantly better than those pre-operative scores, and also better than that of control group (A group) at the same time. But there was no significant difference in scores between 3 months and 6 months in ether B group or C group, and there was also no significant difference in VAS and Oswestry scores between B group and C group at various time points. Various Modic types had no correlation with either VAS score or Oswestry score in each group at various time points. CONCLUSION: Intradiscal interventional therapy can relieve discogenic low back pain and improve Oswestry disability index score of function between 3 and 6 months post-operation. There is no significant difference in post-operative efficacy between Modic Type I and Modic Type II. Steroids are the major analgesic factor of intradiscal injection. But the synergistic application of songmeile (cervus & cucumis polypeptide injection) can maintain the analgesic effect and duration with a decreased dose of steroids.
Assuntos
Deslocamento do Disco Intervertebral/tratamento farmacológico , Dor Lombar/tratamento farmacológico , Adulto , Feminino , Humanos , Injeções Intralesionais , Injeções Espinhais , Deslocamento do Disco Intervertebral/complicações , Dor Lombar/etiologia , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To analyze the selection of surgical methods for lumbar disc herniation with low back and leg pain and degenerative lumbar Modic endplate changes and their different postoperative therapeutic effects. METHODS: All 30 cases of single segment lumbar disc herniation accompanied by Modic endplate changes operated at our hospital using simple discectomy or decompressions with interbody fusion from January 2005 to January 2008 were retrospectively identified. There were 18 males and 12 females with an average age of 38.5 years old (26-53 years old) and an average follow-up of 21 months (4-40 months). RESULTS: Discectomy alone group included 15 cases. The average score of Japanese Orthopedics Association (JOA) and visual analysis scale (VAS) of low back pain and lower extremity radicular pain at the preoperative and final follow-up time was 13.2 (5-17), 6.8 (4-10), 4.8 (1-8) and 19.8 (14 -24), 4.8 (2-10), 1.2 (0-6) respectively. The average improvement rate of JOA was 41.9%. The difference of VAS of lower extremity radicular pain between pre and post-operation was 3.7 on average. Among these 15 cases, Modic I, II and I/II mixed-type was 5, 9, and 1 respectively. Decompression with interbody fusion group included 15 cases. VAS of low back pain and lower extremity radicular pain at the preoperative and final follow-up time was 12.9 (5-17), 7.0 (4-10), 4.9 (1-8) and 22.6 (19-28), 2.8 (2-8) and 1.3 (0-6) respectively. The average improvement rate of JOA was 63.4%. The differences of VAS of lower extremity radicular pain and low back pain between pre and post-operation were 4.3 and 3.6 on average respectively. Among these cases, Modic I, II and I/II mixed-type was 6, 8, and 1 respectively. Comparing the VAS of low back pain, JOA average score and the improvement rate of JOA score of two groups at pre-operation and post-operation, statistical analysis showed that decompression with interbody fusion group was superior to simple discectomy group. CONCLUSION: For lumbar disc herniation with degenerative Modic endplate changes, who suffered more from low back pain than lower extremity radicular pain, discectomy alone and decompression with interbody fusion could both improve the degree of lower extremity radicular pain, but discectomy alone is less likely to improve the degree of low back pain and function score than the latter. So the maneuver of lumbar decompression with fusion is a better choice.