口腔癌 代谢 oral cancer metabolism - PubMed 文献(第 5 页)
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口腔癌 代谢 的 PubMed 搜索结果(第 5 页)
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41. Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer.
41. 探索口腔癌中被DNA高甲基化沉默的肿瘤抑制性微小RNAPMID:日期:2008-04-01[中文摘要] 近年来，微小RNA（miRNA）在分子生物学领域引发了一场革命，并成为癌变过程中的关键参与者。它们已在多种肿瘤类型中被鉴定出来，表明不同的癌症中通常存在不同组合的miRNA失调。为了鉴定口腔鳞状细胞癌（OSCC）特异性的miRNA表达特征，我们首先检测了148种miRNA在18株OSCC细胞系及作为对照的永生化口腔角质形成细胞系RT7中的表达谱。与RT7相比，54种miRNA（36.5%）在OSCC细胞系中频繁下调（表达倍数<0.5倍，在18株细胞系中≥66.7%的细胞系出现下调）。在这54种miRNA中，我们进一步分析了其中四种位于CpG岛附近的miRNA（即miR-34b、miR-137、miR-193a和miR-203），以鉴定通过异常DNA甲基化而沉默的肿瘤抑制性miRNA。在缺乏这四种miRNA表达的OSCC细胞中，经5-氮杂-2'-脱氧胞苷处理后，其表达得以恢复。此外，这四种miRNA的表达水平与OSCC细胞系中其DNA甲基化状态呈负相关。在伴有配对正常口腔黏膜的OSCC原发肿瘤中，通过肿瘤特异性高甲基化导致的miRNA表达下调在miR-137和miR-193a中比在miR-34b和miR-203中更为常见。此外，将miR-137或miR-193a异位转染至缺乏其表达的OSCC细胞系中，可显著抑制细胞生长，并分别伴随细胞周期蛋白依赖性激酶6或E2F转录因子6翻译的下调。综上所述，我们的结果清楚地表明，miR-137和miR-193a是在口腔癌变过程中经表观遗传学沉默的肿瘤抑制性miRNA。
[英文摘要] In the last few years, microRNAs (miRNA) have started a revolution in molecular biology and emerged as key players in the carcinogenesis. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. To identify the miRNA signature that was specific for oral squamous cell carcinoma (OSCC), we first examined expression profiles of 148 miRNAs in a panel of 18 OSCC cell lines and the immortalized oral keratinocyte line RT7 as a control. Compared with RT7, the expression of 54 miRNAs (36.5%) was frequently down-regulated in OSCC lines (<0.5-fold expression, >or=66.7% of 18 lines). Among these 54 miRNAs, we further analyzed four of these miRNAs (i.e., miR-34b, miR-137, miR-193a, and miR-203), located around CpG islands, to identify tumor-suppressive miRNAs silenced through aberrant DNA methylation. The expression of those four genes was restored by treatment with 5-aza-2'-deoxycytidine in OSCC cells lacking their expression. In addition, expression levels of the four miRNAs were inversely correlated with their DNA methylation status in the OSCC lines. In primary tumors of OSCC with paired normal oral mucosa, down-regulation of miRNA expression through tumor-specific hypermethylation was more frequently observed for miR-137 and miR-193a than for miR-34b and miR-203. Moreover, the ectopic transfection of miR-137 or miR-193a into OSCC lines lacking their expressions significantly reduced cell growth, with down-regulation of the translation of cyclin-dependent kinase 6 or E2F transcription factor 6, respectively. Taken together, our results clearly show that miR-137 and miR-193a are tumor suppressor miRNAs epigenetically silenced during oral carcinogenesis.
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42. M2-polarized macrophages contribute to neovasculogenesis, leading to relapse of oral cancer following radiation.
42. M2极化巨噬细胞促进新生血管形成，导致放疗后口腔癌复发PMID:日期:2016-06-08[中文摘要] 尽管放射治疗是口腔癌患者的标准治疗手段之一，但即使在疾病早期，肿瘤仍可能复发，对预后和生活质量造成负面影响。我们此前发现，CD11b(+)骨髓来源细胞（BMDCs）被募集至人多形性胶质母细胞瘤（GBM）中，导致血管结构重塑和肿瘤再生长。然而，这些细胞如何促进肿瘤血管化尚不清楚。在本研究中，我们探讨了浸润性CD11b(+)髓系细胞在口腔鳞状细胞癌（OSCC）血管化及复发中的作用。在异种移植小鼠模型中，局部照射导致肿瘤血管损伤和缺氧，并增加了CD11b(+)髓系细胞的浸润。这些浸润细胞表现出M2型巨噬细胞（M2Mφs）的特征，并与血管化的促进相关。与未照射肿瘤相比，M2Mφs促进了照射后复发肿瘤的进展。此外，我们发现，在人类OSCC标本中，放疗后复发时CD11b(+)髓系细胞以及CD206(+) M2Mφs均增多。我们的发现可能有助于开发针对接受照射的OSCC患者的潜在临床生物标志物或治疗靶点。
[英文摘要] Despite the fact that radiation is one of the standard therapies in the treatment of patients with oral cancer, tumours can recur even in the early stages of the disease, negatively impacting prognosis and quality of life. We previously found that CD11b(+) bone marrow-derived cells (BMDCs) were recruited into human glioblastoma multiforme (GBM), leading to re-organization of the vasculature and tumour regrowth. However, it is not yet known how these cells contribute to tumour vascularization. In the present study, we investigated the role of infiltrating CD11b(+) myeloid cells in the vascularization and recurrence of oral squamous cell carcinoma (OSCC). In a xenograft mouse model, local irradiation caused vascular damage and hypoxia in the tumour and increased infiltration of CD11b(+) myeloid cells. These infiltrating cells showed characteristics of M2 macrophages (M2Mφs) and are associated with the promotion of vascularization. M2Mφs promoted tumour progression in recurrence after irradiation compared to non-irradiated tumours. In addition, we found that CD11b(+) myeloid cells, as well as CD206(+) M2Mφs, are increased during recurrence after radiotherapy in human OSCC specimens. Our findings may lead to the development of potential clinical biomarkers or treatment targets in irradiated OSCC patients.
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43. In Vitro Assessment of the Anticancer Potential of Evodiamine in Human Oral Cancer Cell Lines.
43. 吴茱萸碱在人口腔癌细胞系中抗癌潜力的体外评估PMID:DOI:日期:2015-04-22[中文摘要] 吴茱萸碱是一种具有生物活性的生物碱，被认为具有抗氧化、抗炎和抗癌特性。在本研究中，我们探讨了吴茱萸碱对人源口腔癌细胞系细胞生长和凋亡的影响。我们的数据显示，吴茱萸碱显著抑制人源口腔癌细胞的增殖，并导致PARP（聚（ADP-核糖）聚合酶）和caspase-3的剪切，同时引起典型的凋亡特征。吴茱萸碱还增加了Bax蛋白水平，并引起Bax向线粒体转位及Bax寡聚化。此外，吴茱萸碱在转录修饰水平降低了髓系细胞白血病-1（Mcl-1）的表达，而敲低Mcl-1明显导致Bax和活性Bax表达增加，从而诱导凋亡。吴茱萸碱降低了磷酸化AKT的表达，LY294002通过调控Mcl-1蛋白增强了吴茱萸碱诱导的凋亡。我们的结果表明，吴茱萸碱通过AKT通路诱导人源口腔癌细胞凋亡。这些发现为其临床应用于口腔癌治疗提供了依据。
[英文摘要] Evodiamine, a bioactive alkaloid, has been regarded as having antioxidant, antiinflammatory, and anticancer properties. In the present study, we explored the effects of evodiamine on cell growth and apoptosis in human oral cancer cell lines. Our data revealed that evodiamine significantly inhibited the proliferation of human oral cancer cells and resulted in the cleavages of PARP (poly (ADP-ribose) polymerase) and caspase-3, in addition to causing the typical characteristics of apoptosis. Evodiamine also increased Bax protein levels and caused translocation of Bax into mitochondria and Bax oligomerization. In addition, evodiamine decreased expression of myeloid cell leukemia (Mcl-1) at the transcriptional modification, and knockdown of Mcl-1 clearly resulted in an increase in expression of Bax and active Bax, resulting in induction of apoptosis. Evodiamine reduced expression of phosphorylated AKT, and LY294002 potentiated evodiamine-induced apoptosis by regulating Mcl-1 protein. Our results suggest that evodiamine induces apoptosis in human oral cancer cells through the AKT pathway. These findings provide a rationale for its clinical application in the treatment of oral cancer.
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44. Neutron autoradiography to study boron compound microdistribution in an oral cancer model.
44. 中子放射自显影研究口腔癌模型中硼化合物的微分布PMID:日期:2015-01-24[中文摘要] 我们此前报道了序贯硼中子俘获治疗（Seq-BNCT）在仓鼠颊囊口腔癌模型中的治疗疗效，即先给予BPA（硼苯丙氨酸）-BNCT，1或2天后再给予GB-10（十氢十硼酸盐）-BNCT。我们利用中子放射自显影方法研究组织中的硼微分布。目的是利用该方法评估在序贯BNCT方案中，先前给予BPA-BNCT是否会改变GB-10的分布。对以下各组进行了广泛的定性和定量放射自显影分析：G1组（未给硼的动物）；G2组（注射BPA的动物）；G3组（注射GB-10的动物）；G4组（与G3组相同，但在BPA-BNCT后24小时）；G5组（与G4组方案相同，间隔48小时）。对仓鼠颊囊肿瘤、癌前病变及正常组织的不同组织结构中硼的定位进行了详细研究。GB-10优先蓄积于非肿瘤性结缔组织，而BPA则在肿瘤细胞中显示最高的硼浓度。GB-10的硼分布较BPA异质性更低。在癌前病变和正常组织中，GB-10和BPA分别主要蓄积于结缔组织和上皮。BPA-BNCT可能改变随后给予的GB-10的硼微观定位。硼靶向的均匀性对治疗成功至关重要。
[英文摘要] We previously reported the therapeutic efficacy of Sequential Boron Neutron Capture Therapy (Seq-BNCT), i.e., BPA (boronophenylalanine) - BNCT followed by GB-10 (decahydrodecaborate) - BNCT 1 or 2 days later, in the hamster cheek pouch oral cancer model. We have utilized the neutron autoradiography methodology to study boron microdistribution in tissue. The aim was to use this method to evaluate if the distribution of GB-10 is altered by prior application of BPA-BNCT in Sequential BNCT protocols. Extensive qualitative and quantitative autoradiography analyses were performed in the following groups: G1 (animals without boron); G2 (animals injected with BPA); G3 (animals injected with GB-10); G4 (same as G3, 24 h after BPA-BNCT); and G5 (same protocol as G4, 48 h interval). A detailed study of boron localization in the different tissue structures of tumor, premalignant and normal tissue in the hamster cheek pouch was performed. GB-10 accumulated preferentially in non-neoplastic connective tissue, whereas for BPA neoplastic cells showed the highest boron concentration. Boron distribution was less heterogeneous for GB-10 than for BPA. In premalignant and normal tissue, GB-10 and BPA accumulated mostly in connective tissue and epithelium, respectively. BPA-BNCT could alter boron microlocalization of GB-10 administered subsequently. Boron targeting homogeneity is essential for therapeutic success.
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45. Epigenetic regulation of HOXA3 and its impact on oral squamous cell carcinoma progression.
45. HOXA3的表观遗传调控及其对口腔鳞状细胞癌进展的影响PMID:日期:2024-11-22[中文摘要] 同源盒A3（HOXA3）在癌症进展中的作用日益受到关注，但迄今为止，尚无研究探讨其在口腔癌中的调控功能。在本研究中，我们通过表观遗传学机制探索了HOXA3的作用。临床样本采集自25例潜在恶性口腔病变和50例口腔鳞状细胞癌（OSCC）患者，并分为低分期和高分期肿瘤。通过克隆和荧光素酶实验测定HOXA3的启动子活性。利用甲基化捕获测序鉴定该基因的CpG甲基化模式。采用RT‒qPCR分析基因表达。使用Survminer R包评估3' UTR甲基化与总生存期相关的临床意义。利用RNAInter和TargetScan v8.0分析RNA‒RNA相互作用。HOXA3表达在异型增生中上调，在晚期癌症分期中下调，与启动子甲基化呈负相关，提示DNA甲基化对其的表观遗传调控。3' UTR的高甲基化与晚期阶段较差的总生存期相关。长链非编码RNA和微小RNA可能在口腔癌变过程中对HOXA3进行转录后调控。3' UTR中CpG特异性高甲基化可能作为OSCC的潜在生物标志物。
[英文摘要] The role of homeobox A3 (HOXA3) in cancer progression is gaining prominence, however, to date, no studies have investigated its regulatory function in oral cancer. In this study, we explored the role of HOXA3 through epigenetic mechanisms. Clinical samples were collected from 25 potentially malignant oral lesions and 50 oral squamous cell carcinoma (OSCC) patients, categorized into low-stage and high-stage tumors. The promoter activity of HOXA3 was determined through cloning and luciferase assays. CpG methylation patterns across the gene were identified using methyl-capture sequencing. Gene expression was analyzed using RT‒qPCR. The Survminer R package was used to assess the clinical significance of 3' UTR methylation associated with overall survival. RNA‒RNA interactions were analyzed using RNAInter and TargetScan v8.0. HOXA3 expression was upregulated in dysplasia and downregulated in advanced cancer stages, showing an inverse correlation with promoter methylation, suggesting epigenetic regulation by DNA methylation. Hypermethylation of the 3' UTR was associated with poor overall survival in advanced stages. Long noncoding RNAs and microRNAs may post-transcriptionally modulate HOXA3 in oral carcinogenesis. CpG-specific hypermethylation in the 3' UTR may serve as a potential biomarker in OSCC.
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46. Identification of lysine acetylome of oral squamous cell carcinoma by label-free quantitative proteomics.
46. 通过无标记定量蛋白质组学鉴定口腔鳞状细胞癌赖氨酸乙酰化组PMID:日期:2022-04-27[中文摘要] 组蛋白赖氨酸乙酰化（Kac）可促进染色质构象松弛，有利于基因转录，从而调控肿瘤发生，但口腔鳞状细胞癌（OSCC）的整体乙酰化图谱尚不清楚。采用液相色谱-串联质谱（LC-MS/MS）技术研究9例OSCC患者肿瘤组织及癌旁正常组织的赖氨酸乙酰化特征。在OSCC组织与配对癌旁正常组织之间，共鉴定出234个蛋白中的282个上调Kac位点以及162个蛋白中的235个下调Kac位点。通过基于KEGG和MCODE的分析对差异乙酰化蛋白（DAPs）进行研究。这些DAPs富集于核糖体生物发生通路。利用TCGA数据库对枢纽基因进行生存分析。此外，使用IPA软件探讨9个核心DAPs（RPS3、RPL24、RPL19、EIF4A2、RPL12、MYBPC1、RPS6、ARCN1和TMEM9）与蛋白质组学中鉴定到的KATs和KDACs差异表达之间的联系。本研究是首个针对口腔鳞状细胞癌Kac修饰的比较研究。我们提出假说：赖氨酸乙酰化改变，尤其是RPS6和RPS3乙酰化下调所导致的核糖体生物发生功能障碍，可能与OSCC的发病机制相关。意义：本研究是首个通过基于LC-MS/MS的修饰蛋白质组学对口腔鳞状细胞癌Kac修饰进行的比较研究。这些DAPs高度富集于核糖体生物发生通路。利用MCODE和生存分析，筛选出9个核心DAPs（RPS3、RPL24、RPL19、EIF4A2、RPL12、MYBPC1、RPS6、ARCN1和TMEM9）。使用IPA软件探讨9个核心DAPs与蛋白质组学中鉴定到的KATs和KDACs差异表达之间的联系。此外，我们提出假说：赖氨酸乙酰化改变，尤其是RPS6和RPS3乙酰化下调所导致的核糖体生物发生功能障碍，可能与OSCC的发病机制相关。
[英文摘要] Lysine acetylation (Kac) on histone promotes relaxation of the chromatin conformation and favors gene transcription to regulate oncogenesis, whereas the total acetylation profiling of oral squamous cell carcinoma (OSCC) is unknown. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilised to investigate lysine acetylation features of tumor tissues and adjacent normal tissues from 9 patients with OCSS. 282 upregulated Kac sites in 234 proteins and 235 downregulated Kac sites in 162 proteins between OSCC tissues and paired adjacent normal tissues were identified. Different acetylation proteins (DAPs) were analyzed through KEGG-based and MCODE. These DAPs are enriched in the ribosome biogenesis pathway. Survival Analysis of hub genes with TCGA database was performed. In addition, IPA software was used to explore the connection between 9 core DAPs (RPS3, RPL24, RPL19, EIF4A2, RPL12, MYBPC1, RPS6, ARCN1, and TMEM9) and the different expression of KATs and KDACs identified in our proteomic. The study is the first comparative study of Kac modification on oral squamous cell carcinoma. We propose to put forward the hypothesis that the dysfunction of ribosome biogenesis caused by the change of Lysine acetylation, especially downregulated acetylation on RPS6 and RPS3 may associated with the pathogenesis of OSCC. SIGNIFICANCE: The study is the first comparative study of Kac modification on oral squamous cell carcinoma through LC-MS/MS-based modified proteomic. These DAPs are high enriched in the ribosome biogenesis pathway. Used MCODE and survival analysis, 9 core DAPs (RPS3, RPL24, RPL19, EIF4A2, RPL12, MYBPC1, RPS6, ARCN1, and TMEM9) were screened. IPA software was used to explore the connection between 9 core DAPs and the different expression of KATs and KDACs identified in our proteomic. In addition, we propose to put forward the hypothesis that the dysfunction of ribosome biogenesis caused by the change of Lysine acetylation, especially downregulated acetylation on RPS6 and RPS3 may associated with the pathogenesis of OSCC.
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47. The early manifestation, tumor-specific occurrence and prognostic significance of TGFBR2 aberrant splicing in oral carcinoma.
47. 口腔癌中TGFBR2异常剪接的早期表现、肿瘤特异性发生及预后意义PMID:日期:2014-05-15[中文摘要] 可变剪接是一种重要机制，可破坏细胞周期调控，从而导致肿瘤发生。尽管在癌症中已报道了转化生长因子β（TGFβ）信号通路的许多改变，但剪接异常在破坏该信号通路稳定性中的作用却是了解最少的机制。在本研究中，我们比较了潜在恶性口腔疾病（PMDs）和口腔鳞状细胞癌（OSCC）样本与正常样本中的TGFBR2可变剪接事件。有趣的是，在OSCC中存在五种激酶结构域缺陷的TGFBR2可变剪接形式。TGFBR2异常剪接具有肿瘤特异性，提示选择性剪接去除TGFBR2激酶结构域可能是癌细胞用以逃避TGFβ信号介导的抗肿瘤活性的一种机制。此外，这些异常转录本也存在于PMDs中，提示这些事件在口腔癌变过程中早期发生，并为恶性肿瘤的早期诊断提供了可能性。此外，携带这些异常剪接转录本的OSCC患者表现出较差的无病生存期（p=0.028）和较差的总生存期（p=0.013）。因此，评估这些TGFBR2转录本的存在可作为口腔癌的预后标志物。
[英文摘要] Alternative splicing is an important mechanism that can disrupt cell cycle control resulting in tumorigenesis. Although many alterations of Transforming Growth Factor Beta (TGFβ) signaling are reported in cancers, the role of splice aberrations in destabilizing this signaling is the least understood mechanism. In this study, we compared TGFBR2 alternative splicing events in potentially malignant oral disorders (PMDs) and oral squamous cell carcinoma (OSCC) samples with those in normal samples. Interestingly, there were five alternatively spliced forms of TGFBR2 with a deficient kinase domain in OSCCs. The TGFBR2 aberrant splicing was tumor-specific, suggesting that selective splicing out of TGFBR2 kinase domain could be a mechanism misused by cancer cells for evading TGFβ signaling-mediated anti-tumor activities. Moreover, these aberrant transcripts were present in PMDs as well, suggesting an early occurrence of these events during oral carcinogenesis and offering the possibility of early diagnosis of malignancy. Furthermore, OSCC patients who harbored these aberrantly spliced transcripts exhibited poor disease free survival (p=0.028) and poor overall survival (p=0.013). Thus, assessing the presence of these TGFBR2 transcripts can serve as a prognostic marker for oral cancer.
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48. B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway.
48. B细胞淋巴瘤/白血病10通过STAT1/ATF4/S100P信号通路促进口腔癌进展PMID:日期:2014-03-31[中文摘要] B细胞淋巴瘤/白血病10（BCL10）是一种凋亡调节蛋白，与口腔鳞状细胞癌（OSCC）的晚期TNM分期和疾病复发相关。然而，BCL10在OSCC进展中的调控机制仍不清楚。本研究中，我们发现敲低内源性BCL10可显著降低细胞迁移和侵袭能力，通过G0/G1期阻滞延缓细胞增殖，并在体内抑制致瘤性。在分子水平上，我们通过高通量微阵列分析鉴定出S100P是BCL10抑制OSCC进展的关键下游效应分子。在BCL10沉默克隆中，S100P信使RNA和蛋白表达水平显著降低，而转染S100P表达质粒可恢复shBCL10转染细胞的迁移、侵袭、增殖能力及致瘤性。此外，我们提供证据表明BCL10通过信号转导子和转录激活因子1（STAT1）及激活转录因子4（ATF4）调控S100P表达。敲低BCL10降低了S100P启动子活性，但在截短的STAT1/ATF4 S100P启动子中无影响。此外，我们还发现P50/P65信号通路参与了BCL10增强的OSCC进展。在BCL10沉默克隆中恢复S100P可通过由外向内信号显著逆转P65活化。综上所述，我们发现了一条通过STAT1/ATF4/S100P/P65信号轴调控OSCC进展的新通路，该通路可预测OSCC预后，并有助于制定针对晚期OSCC的治疗策略。
[英文摘要] B-cell lymphoma/leukemia 10 (BCL10) is an apoptotic regulatory protein related to advanced TNM stage and disease recurrence in oral squamous cell carcinoma (OSCC). However, the regulatory mechanism of BCL10 in OSCC progression is still unknown. Here, we showed that knockdown of endogenous BCL10 could significantly reduce cell migration and invasion abilities, retard cell proliferation by G0/G1 phase accumulation and inhibit tumorigenicity in vivo. In molecular level, we identified S100P as a crucial downstream effector of BCL10-inhibited OSCC progression by high-throughput microarray analysis. S100P messenger RNA and protein expression levels were significantly diminished in silenced-BCL10 clones, and transfected S100P expression plasmids restored migration, invasion, proliferation abilities and tumorigenicity in shBCL10 transfectants. Furthermore, we provided evidence that BCL10 regulated S100P expression through signal transducers and activators of transcription 1 (STAT1) and activating transcription factor 4 (ATF4). Knockdown of BCL10 decreased S100P promoter activity, but showed no effect in truncated STAT1/ATF4 S100P promoter. In addition, we also found that the P50/P65 signaling pathway was involved in BCL10-enhanced OSCC progression. Restored S100P in silenced-BCL10 clones could markedly reverse P65 activation via outside-in signaling. Taken together, we discovered a novel axis of BCL10-regulated OSCC progression via STAT1/ATF4/S100P/P65 signaling, which could predict the prognosis of OSCC and will be beneficial for developing therapeutic strategy against advanced OSCC.
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49. Quantitative detection of circulating tumor-derived mitochondrial NADH subunit variants as a potential prognostic biomarker for oral cancer.
49. 循环肿瘤来源线粒体NADH亚基变异的定量检测作为口腔癌潜在预后生物标志物PMID:日期:2015-07-15[中文摘要] 循环肿瘤细胞（CTCs）和/或其相关分子是癌症治疗过程中有前景的决定因素，尤其对于治疗后监测。我们最近报道了在口腔鳞状细胞癌（OSCCs）中检测三个不同区域（包括置换环、12S-rRNA和16S-rRNA）的循环肿瘤相关突变线粒体DNA（mut-mtDNAs）的临床意义。在本研究中，为进一步探讨其他mut-mtDNAs是否具有检测潜在肿瘤微转移的新效能，我们通过定量实时PCR结合高分辨率熔解曲线分析，对来自240份OSCC患者临床样本中基因组ND2和ND3区域的mut-mtDNAs进行了体外和体内评估。此外，通过受试者工作特征曲线下面积（AUC）分析评估其临床意义。在OSCC来源的细胞系中，于ND2区域（5108位点T:A突变为C:G）和ND3区域（10397位点A:T突变为G:C及10400位点C:G突变为T:A）鉴定出三个离散的序列变异，而在正常对照人正常口腔角质形成细胞中未观察到突变。在所检测的OSCC患者中，术后期间血清中mut-mtDNAs的存在准确预测了不良预后（ND2 AUC，0.761；ND3 AUC，0.704）。本文所呈现的数据提供了一种检测循环mut-mtDNAs的新方法，这些分子标志物有望用于评估OSCCs中的肿瘤微转移。
[英文摘要] Circulating tumor cells (CTCs) and/or their relating molecules are promising determinants during the course of cancer treatment, especially for post-therapeutic monitoring. We recently reported the clinical relevance of detecting circulating tumor-associated mutant mitochondrial DNAs (mut-mtDNAs) at three different regions including the displacement loop, 12S-rRNA and 16S-rRNA in oral squamous cell carcinomas (OSCCs). In the present study, to further investigate if the other mut-mtDNAs have novel efficiency for detecting potential tumoral micrometastasis, mut-mtDNAs on the ND2 and ND3 regions of the genome in 240 clinical samples from patients with OSCC were assessed in vitro and in vivo by quantitative real-time PCR combined with high-resolution melting curve analysis. Furthermore, the clinical relevance was evaluated by the area under the receiver operating characteristic curve (AUC) analysis. Three discrete sequence variations were identified in OSCC derived cell lines at the regions of ND2 (T:A to C:G at position 5108) and ND3 (A:T to G:C at position 10397 and C:G to T:A at position 10400), whereas no mutation was observed in normal control human normal oral keratinocytes. In OSCC patients examined, the presence of mut-mtDNAs in serum during the postoperative period accurately predicted poor prognoses (ND2 AUC, 0.761; ND3 AUC, 0.704). The data presented here provide a novel approach for detecting the circulating mut-mtDNAs that are promising molecular markers for evaluating tumoral micrometastasis in OSCCs.
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50. Glycolysis reprogramming in cancer-associated fibroblasts promotes the growth of oral cancer through the lncRNA H19/miR-675-5p/PFKFB3 signaling pathway.
50. 癌相关成纤维细胞中的糖酵解重编程通过lncRNA H19/miR-675-5p/PFKFB3信号通路促进口腔癌生长PMID:日期:2021-03-25[中文摘要] 作为肿瘤微环境的重要组成部分，肿瘤相关成纤维细胞（CAFs）通过分泌能量代谢产物为肿瘤进展提供能量。长链非编码RNA（lncRNA）的异常调控被认为参与葡萄糖代谢，但lncRNA在口腔CAFs糖酵解中的作用尚未被系统研究。在本研究中，我们利用RNA测序和生物信息学分析，分析了来源于正常组织的正常成纤维细胞（NFs）和来源于口腔鳞状细胞癌（OSCC）患者的CAFs的lncRNA/mRNA表达谱。LncRNA H19被鉴定为口腔CAFs中的关键lncRNA，并在口腔癌细胞系和CAFs中同步上调。利用小干扰RNA（siRNA）策略，我们确定敲低lncRNA H19可影响口腔CAFs的增殖、迁移和糖酵解。我们发现，siRNA敲低lncRNA H19可抑制MAPK信号通路、6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3（PFKFB3）以及miR-675-5p。此外，通过荧光素酶报告系统实验和miRNA特异性抑制剂处理证实，lncRNA H19/miR-675-5p/PFKFB3轴参与促进口腔CAFs中的糖酵解途径。我们的研究为理解口腔CAFs中的葡萄糖代谢提供了新途径，在理论上为OSCC分子诊断提供了新的生物标志物，并为抗肿瘤治疗提供了新靶点。
[英文摘要] As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.