Retracted Article: Salvianolic acid B inhibits inflammatory response and cell apoptosis via the PI3K/Akt signaling pathway in IL-1β-induced osteoarthritis chondrocytes

Osteoarthritis (OA) is the most common joint disease among late middle-aged or elderly people. The pathological process of OA mainly involves the degeneration of cartilage tissue and deficiency of joint function. Salvianolic acid B (Sal B) is the main active ingredient of Salvia miltiorrhiza Bge, which possesses anti-inflammatory, anti apoptotic and other pharmacological activities. In this study, primary chondrocytes were cultured to investigate the effects of Sal B on the inflammatory response and apoptosis of OA induced by IL-1β, and to explore the possible mechanism. First, we determined the cytotoxicity of Sal B; the results showed that the cell activity of chondrocytes was not influenced by Sal B when the concentration was below 150 μM. Moreover, Sal B (40 and 80 μM) suppressed the expression of iNOS in OA chondrocytes induced by IL-1β, and restrained the secretion of NO, IL-6, IL-17 and TNF-α in chondrocytes obviously. Sal B (40, 80 μM) significantly alleviated the inhibitory effect of cell activity stimulated by IL-1β and up-regulated the expression of Col II and reduced the expression of Col X. Besides, Sal B down-regulated the expression level of Bax and promoted the expression of Bcl-2, showed a significant effect on promoting proliferation and inhibiting cell apoptosis. In addition, we found that IL-1β significantly reduced the ratio of p-PI3K/PI3K, p-Akt/Akt induced the nuclear translocation of AKT and inhibited the activation of the PI3K/Akt signaling pathway. Finally, the PI3K inhibitor, LY-294002, was added in IL-1β-induced chondrocytes. The results suggest that Sal B ameliorates IL-1β induced inflammation and suppresses apoptosis in OA by activating the PI3K/Akt signaling pathway. Our study reveals the mechanism of Sal B acts on OA and may provide a basis for the treatment of OA with Sal B.

Osteoarthritis (OA) is the most common joint disease among late middle-aged or elderly people.     

β-Escin inhibits the proliferation of osteosarcoma cells via blocking the PI3K/Akt pathway

β-Escin exhibits anticancer effects on a panel of established cancer cells. However, the effects of β-escin on human osteosarcoma (OS) are still unknown. The aim of the present study was to investigate whether β-escin was effective against OS both in vivo and in vitro. Our results showed that β-escin induced dose- and time-dependent effects against MG-63, OS732, U-2OS, HOS and SAOS-2 cell proliferation. β-Escin also exhibited excellent anti-proliferative and pro-apoptotic effects in an established OS xenograft model. β-Escin and cytotoxic drugs, including cisplatin, methotrexate (MTX), doxorubicin (Dox) and ifosfamide (Ifos), synergistically inhibited proliferation of MG-63 and OS732 cells in vitro. Moreover, β-escin induced apoptotic death, activated caspase-3, caspase-8 and caspase-9, and regulated expression of Bax and Bcl-2 in MG-63 cells. In addition, our results showed that β-escin treatment reduced expression of p-PI3K, p-Akt and p-mTOR both in MG-63 cells and in an MG-63 xenograft OS model. Interestingly, SC79, which is an Akt activator, inhibited the anti-proliferative effects of β-escin on MG-63 cells. Taken together, our data support the conclusion that β-escin effectively inhibits OS proliferation both in vivo and in vitro. The inhibitory effect of β-escin, at least in part, is due to the inactivation of the PI3K/Akt signalling pathway.

β-Escin exhibits anticancer effects on a panel of established cancer cells. However, the effects of β-escin on human osteosarcoma (OS) are still unknown.     

Retracted Article: Resveratrol attenuates inflammation and reduces matrix-metalloprotease expression by inducing autophagy via suppressing the Wnt/β-catenin signaling pathway in IL-1β-induced osteoarthritis chondrocytes

Resveratrol (Res), a naturally occurring polyphenolic compound, has been reported to exert many biological effects like anti-inflammatory and anti-oxidant effects. In this study, we investigated the role of Res on IL-1β-induced osteoarthritis (OA) chondrocytes and its possible mechanism. Results demonstrated that Res suppressed IL-1β-induced IL-1, IL-6 and TNF-α production in a dose-dependent manner. Res also decreased MMP-1, MMP-3 and MMP-13 production in IL-1β-induced OA chondrocytes. These results suggested that Res suppressed IL-1β-induced inflammation and matrix-metalloproteases (MMP) expression in OA chondrocytes. In addition, Res was found to reverse the decreased autophagy level through increasing the expression of Beclin1, LC3 II/I ratio and LC3⁺ puncta in IL-1β-induced OA chondrocytes. Inhibition of autophagy by 3-methyladenine (3-MA) abolished the inhibitory effect of Res on inflammation and MMP expression in IL-1β-induced OA chondrocytes. Moreover, the Wnt/β-catenin signaling pathway was activated in IL-1β-induced OA chondrocytes. However, Res was found to suppress this activated Wnt/β-catenin signaling pathway. Activation of the Wnt/β-catenin signaling pathway counteracted the promoted effect on autophagy and inhibitory effect on inflammation and MMP expression of Res in IL-1β-induced OA chondrocytes. Taken together, our data demonstrated that Res attenuated inflammation and reduced MMP expression through inducing autophagy via inhibiting the Wnt/β-catenin signaling pathway in IL-1β-induced OA chondrocytes. Res may be used as a potential therapeutic agent for OA treatment.

Resveratrol (Res), a naturally occurring polyphenolic compound, has been reported to exert many biological effects like anti-inflammatory and anti-oxidant effects.     

低强度脉冲超声经PI3K/Akt通路调控兔膝骨性关节炎软骨细胞凋亡的作用机制研究

目的:探讨低强度脉冲超声(LIPUS)对兔膝骨性关节炎(OA)软骨细胞凋亡的影响及有关作用机制。方法:共选取30只新西兰大白兔,随机分为正常对照组(A组)、OA模型组(B组)、OA+LIPUS组(C组)、OA+LY294002(PI3K/Akt抑制剂)组(D组)、OA+LY294002+LIPUS组(E组),每组各6只。采用右后膝前交叉韧带切断术(ACLT)造模。于造模后第6周时采用空气栓塞法处死实验兔,切取软骨组织进行组织学观察,并进行Mankin评分;提取软骨细胞进行体外培养并采用免疫组化染色法鉴定;应用western blot检测各组软骨细胞中Ⅱ型胶原(COL2)、MMP-13、Akt、pAkt、P53、Bcl-2蛋白表达情况。结果:B组COL2、pAkt、Bcl-2蛋白含量较A组降低,MMP-13、P53蛋白含量较A组增高(P<0.05)。与B组相比,C组COL2、pAkt、Bcl-2蛋白含量增高,MMP-13、P53蛋白含量下降(P<0.05);D组COL2、Bcl-2、pAkt蛋白含量下降,MMP-13、P53蛋白含量升高(P<0.05),E组COL2、MMP-13、P53、Bcl-2、pAkt蛋白含量无明显变化,但与C组、D组相比差异显著(P<0.05)。各组Akt蛋白表达无明显差异。结论:LIPUS能通过PI3K/Akt通路降低兔膝骨性关节炎软骨细胞凋亡率,促进抗凋亡基因Bcl-2表达,下调促凋亡基因P53水平,促进关节软骨损伤修复。     

Down-regulation of HOXB5 inhibits TGF-β-induced migration and invasion in hepatocellular carcinoma cells via inactivation of the PI3K/Akt pathway

HOXB5, a member of the HOX gene family, is a developmental gene which encodes homeoproteins and is known to be a crucial player in development of enteric nervous systems. Recently, HOXB5 was reported to be associated with cancer progression. However, the specific effect of HOXB5 in hepatocellular carcinoma (HCC) remains unclear. In this study, we demonstrated the important role of HOXB5 in HCC. We showed that HOXB5 was up-regulated in HCC tissues and cell lines. Furthermore, down-regulation of HOXB5 inhibited TGF-β-induced HCC cell migration and invasion in vitro and suppressed tumor metastasis in vivo. We also found that the PI3K/Akt pathway partly accounted for the mechanisms underlying the inhibitory effect of HOXB5 down-regulation on TGF-β-induced HCC progression. Taken together, these findings demonstrated that down-regulation of HOXB5 inhibits TGF-β-induced migration and invasion in HCC cells via inactivation of the PI3K/Akt pathway. Thus, HOXB5 may be a novel therapeutic target for HCC treatment.

HOXB5, a member of the HOX gene family, is a developmental gene which encodes homeoproteins and is known to be a crucial player in development of enteric nervous systems.     

EGFR/PI3K/Akt细胞信号传导通路与肿瘤

表皮生长因子受体(EGFR)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(PKB,也称Akt)信号通路是生物体内一条非常重要的生存信号通路。EGFR通过二聚化后刺激Ras蛋白,导致磷酸化级联反应的发生来激活PI3K/Akt信号通路,从而引起肿瘤的发生发展。本文从EGFR/PI3K/Akt信号传导通路对肿瘤的调节机制等多个方面综述了EGFR/PI3K/Akt信号通路与肿瘤的关系。     

PI3K/Akt信号通路与脑出血的研究进展

磷脂酰激醇3-激酶（PI3K）/蛋白激酶B（Akt）信号通路作为经典的细胞信号转导途径,在细胞生长、增殖、分化和凋亡等多种生物学过程中发挥作用。脑出血是一种高致残率和高致死率的脑血管疾病,该通路在脑出血发生发展中的研究也备受关注。该文以PI3K/Akt信号通路为主线,对该通路的结构及生物学特点、与脑出血之间的关系以及基于该通路探讨药物对脑出血的作用进行综述,为临床脑出血的治疗提供新的思路。     

Retracted Article: Down-regulation of Rab10 inhibits hypoxia-induced invasion and EMT in thyroid cancer cells by targeting HIF-1α through the PI3K/Akt pathway

Rab10, a member of the Rab family, is localized to endocytic compartments and serves as a regulator of intracellular vesicle trafficking. Previous studies mainly paid attention to the role of Rab10 in transport. Recently, Rab10 has been reported to be involved in the progression of various cancers. However, the biological functions of Rab10 in thyroid cancer remain unknown. In this study, we demonstrated that Rab10 was highly expressed in thyroid cancer tissues and cell lines. Down-regulation of Rab10 inhibited hypoxia-induced migration, invasion and epithelial–mesenchymal transition (EMT) of thyroid cancer cells. Moreover, HIF-1α and the PI3K/Akt pathway were involved in the inhibitory effect of Rab10 down-regulation on thyroid cancer cell invasion and EMT induced by hypoxia. Taken together, our study provided further evidence to support the role of Rab10 as a therapeutic target for thyroid cancer.

Rab10, a member of the Rab family, is localized to endocytic compartments and serves as a regulator of intracellular vesicle trafficking.     

PI3K/Akt信号通路在肝脏缺血再灌注损伤中的研究进展

肝脏缺血再灌注损伤是导致术后肝脏功能延迟恢复和功能障碍的重要原因。有研究表明,PI3K/Akt信号通路在缺血和再灌注的过程中被激活,通过抑制或增强下游相关靶蛋白的表达发挥对肝脏的保护作用。因此,PI3K/Akt信号成为预防和改善肝脏缺血再灌注损伤的重要靶向通路。本文就PI3K/Akt信号通路在肝脏缺血再灌注损伤中作用的研究进展进行综述。     

骨形态发生蛋白7通过PI3K/Akt通路可抑制人髓核细胞的凋亡

背景：骨形态发生蛋白7可促进人髓核细胞的细胞外基质合成,减缓椎间盘退变.近年来,有学者提出其可能通过对抗髓核细胞凋亡从而发挥上述作用,但其进一步的分子机制一直未被详细阐明.目的：观察骨形态发生蛋白7对无血清诱导下发生凋亡的人髓核细胞产生的作用及其对PI3K/Akt通路的影响,分析并探讨骨形态发生蛋白7抑制人髓核细胞凋亡的分子机制.方法：通过改良Pfirrmann分级及相关条件选取12例患者获取椎间盘组织,采用酶消化法获取人髓核细胞后分组实验,以含体积分数15％胎牛血清的培养基正常培养的髓核细胞设为空白组;使用无血清培养基培养48 h诱导凋亡作为阳性对照组;在无血清条件下,通过加入不同剂量的骨形态发生蛋白7以及同时添加PI3K/Akt通路拮抗剂LY294002形成处理组和拮抗组.使用流式细胞术检测各组细胞凋亡率;免疫荧光观察p-Akt表达;蛋白印迹法检测Akt,p-Akt,BAD和Caspase 9等通路蛋白的表达变化.结果与结论：无血清凋亡诱导下,流式细胞术结果显示,随着骨形态发生蛋白7处理浓度上升,髓核细胞凋亡率明显下降,加入LY294002共同作用后细胞凋亡率再次升高（P＜0.05）.p-Akt免疫荧光和蛋白印迹法检测结果进一步表明,与凋亡阳性对照组相比,加入骨形态发生蛋白7的实验组中,p-Akt表达明显增加,其下游凋亡相关蛋白BAD、Caspase 9蛋白表达减少（P＜0.05）,而在同时加入Akt通路拮抗剂LY294002后,p-Akt蛋白表达下降而凋亡相关蛋白的表达又恢复到相对较高的水平（P＜0.05）.结果证明,骨形态发生蛋白7在无血清诱导的人类髓核细胞凋亡中通过激活PI3K/Akt通路,拮抗了BAD-Caspase 9相关的细胞凋亡过程,抑制了髓核细胞的退变.     

Notoginsenoside R1 prevents H9c2 cardiomyocytes apoptosis against hypoxia/reoxygenation via the ERs/PI3K/Akt pathway

Notoginsenoside R₁ (NGR₁) is separate from Panax notoginsenosides (PNS), and plays a role similar to phytoestrogen in preventing and treating cardiovascular diseases. However, the protective mechanism of NGR₁ in the myocardial ischemia/reperfusion injury via the estrogen receptor (ER) pathway remains unclear, which hinder its application. This study aimed to study the preventive mechanisms of NGR₁ in the apoptosis of H9c2 cardiomyocytes after hypoxia/reoxygenation (H/R). NGR₁ did not affect the expression of ERα and ERβ proteins in normal H9c2 cardiomyocytes. However, NGR₁ could upregulate the ERα and G protein-coupled receptor 30 (GPR30) proteins in H9c2 cardiomyocytes after H/R without affecting ERβ levels. Moreover, it significantly affected the expression levels of PI3K and its downstream apoptosis proteins such as Bcl-2 Associated X Protein (Bax), B cell lymphoma/lewkmia-2 (Bcl-2), caspase-3, and so forth. Whereas, after adding the PI3K protein antagonist, the modulatory expression levels of PI3K and its downstream apoptosis proteins were remarkably abolished. After adding ERα and GPR30 antagonists, NGR₁ had no significant effect on the expression of PI3K and its downstream Akt protein in the model group. The data of flow cytometry showed that after adding the ERα, GPR30 and PI3K antagonists, the apoptotic rate of cardiomyocytes had no significant changes compared with the model group. This study demonstrated that NGR₁ protected H9c2 cardiomyocytes from the injury after H/R by affecting ERα and GPR30 to regulate the expression levels of PI3K and its downstream apoptosis proteins.

Notoginsenoside R₁ (NGR₁) is separate from Panax notoginsenosides (PNS), and plays a role similar to phytoestrogen in preventing and treating cardiovascular diseases.     

磷脂酰肌醇-3激酶/蛋白激酶B信号通路在肝细胞癌和靶向药耐药中作用研究进展

磷脂酰肌醇-3-激酶/蛋白激酶B信号通路是影响肿瘤细胞增殖、凋亡、侵袭转移及化疗耐药的重要信号转导通路.肝细胞癌中存在磷脂酰肌醇-3-激酶/蛋白激酶B信号通路的传导异常.本文就磷脂酰肌醇-3-激酶/蛋白激酶B信号通路的功能、激活途径、在肝细胞癌进展及其对肝细胞癌靶向药耐药中作用的研究进展作一综述.     

Tamoxifen reduces P-gp-mediated multidrug resistance via inhibiting the PI3K/Akt signaling pathway in ER-negative human gastric cancer cells

Multidrug resistance (MDR), mediated by overexpression of drug efflux transporters such as P-glycoprotein (P-gp), is a major problem limiting successful chemotherapy of gastric cancer. Tamoxifen (TAM), a triphenylethylene nonsteroidal antiestrogen agent, shows broad-spectrum antitumor properties. Emerging studies demonstrated that TAM could significantly reduce the MDR in a variety of human cancers. Here we investigated the effects and possible underlying mechanisms of action of TAM on the reversion of MDR in ER-negative human gastric cancer cells. Our results demonstrated that in MDR phenotype SGC7901/CDDP gastric cancer cells TAM dramatically lowered the IC₅₀ of CDDP, 5-FU and ADM, increased the intracellular Rhodamine123 accumulation and induced G0/G1 phase arrest, while G2/M phase decreased accordingly. Furthermore, at the molecular level, TAM substantially decreased the expression of P-gp, p-Akt and the Akt-regulated downstream effectors such as p-GSK-3β, p-BAD, Bcl-XL and cyclinD1 proteins without affecting the expression of t-Akt, t-GSK-3β, t-BAD proteins in SGC7901/CDDP cells. Thus, our findings demonstrate that TAM reverses P-gp-mediated gastric cancer cell MDR via inhibiting the PI3K/Akt signaling pathway.     

Retracted Article: Daphnetin inhibits proliferation and glycolysis in colorectal cancer cells by regulating the PI3K/Akt signaling pathway

Daphnetin (7,8-dihydroxycoumarin), a natural coumarin compound, has shown antitumor and energy metabolism regulatory activities. However, the effects of daphnetin on cell proliferation, migration, and glucose metabolism in colorectal cancer (CRC) cells remains unknown. In this study, the effects of daphnetin on CRC cell proliferation, migration, and glucose metabolism have been examined. The results showed that daphnetin inhibited the proliferation, migration, and invasion of CRC cells, and induced CRC cell apoptosis. Furthermore, daphnetin suppressed intracellular glucose and lactate production, and downregulated the expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) in CRC cells. Furthermore, daphnetin prevented activation of the PI3K/Akt pathway in CRC cells. These findings demonstrated that daphnetin inhibited the proliferation, migration and glucose metabolism in CRC cells by suppressing the PI3K/Akt signaling pathway. Therefore, daphnetin has potential as a novel anticancer agent for CRC treatment.

Daphnetin (7,8-dihydroxycoumarin), a natural coumarin compound, has shown antitumor and energy metabolism regulatory activities.     

肠三叶因子介导PI3K/Akt信号通路保护胃黏膜上皮细胞紧密连接

目的：探讨肠三叶因子对胃黏膜上皮细胞紧密连接的保护作用,并研究PI3K/Akt信号通路在其中的作用机制。方法：体外培养GES-1细胞,分别设正常对照组,LPS组,ITF组,LPS＋ITF组,LPS＋ITF＋LY294002组,ITF＋LY294002组。正常对照组：正常培养;LPS组：加入浓度为10mg/L的LPS;ITF组：加入浓度为100μg/L的ITF;LPS＋ITF组：加入浓度为10mg/L的LPS,同时加入100μg/L的ITF;LPS＋ITF＋LY294002组：加入浓度为10mg/L的LPS、100μg/L的ITF,同时加入PI3K/Akt信号通路的抑制剂LY294002（15μM）;ITF＋LY294002组：加入100μg/L的ITF,同时加入15μM的LY294002。培养48h,采用Western blot检测ITF对PI3K/Akt信号通路的作用,采用免疫荧光和Western blot检测细胞紧密连接蛋白Occludin和ZO-1的变化情况。结果：Western blot检测结果说明,与对照组相比,ITF提高了pAkt蛋白的表达水平,而LY294002抑制了ITF激活的pAkt蛋白的表达,说明ITF可以通过激活PI3K/Akt信号通路来调控GES-1细胞的生理活动。免疫荧光和Western blot结果显示LPS导致GES-1细胞的紧密连接遭到破坏,降低紧密连接蛋白Occludin和ZO-1的表达水平,而ITF可以通过激活PI3K/Akt信号通路来保护GES-1细胞的紧密连接的完整性。结论：ITF保护胃黏膜上皮细胞紧密连接的完整性,提高紧密连接蛋白的表达水平,其发挥作用的主要分子机制是通过激活PI3K/Akt信号通路来实现的。     

Silencing of lncRNA MIR31HG promotes nasopharyngeal carcinoma cell proliferation and inhibits apoptosis through suppressing the PI3K/AKT signaling pathway

BackgroundMIR31HG has been affirmed to regulate the tumorigenesis of head–neck squamous cell carcinoma (HNSC). This study aims to reveal the function of MIR31HG in nasopharyngeal carcinoma (NPC), which falls into the category of HNSC.MethodsMIR31HG expression pattern in HNSC tissues was predicted by starBase. FISH and qRT‐PCR were employed to detect MIR31HG expression in NPC tissues and to analyze the association between MIR31HG and clinicopathological features. NPC cell viability, colony formation, and apoptosis were measured by MTT assay, colony formation assay, and flow cytometry. The expressions of protein kinase B (AKT), phosphorylated (p)‐AKT, phosphoinositide 3‐kinases (PI3K) and p‐PI3K in NPC cells were analyzed by Western blot. The correlation between MIR31HG expression and AKT1 mRNA expression was analyzed by The Cancer Genome Atlas and starBase.ResultsMIR31HG was highly expressed in HNSC tissues and NPC tissues. Meanwhile, the association between high MIR31HG expression and aggressive clinicopathological traits was significant in NPC patients at tumor stage III‐IV (T3‐T4) and in those with lymph node metastasis 1–2 (N1‐N2). Silencing of MIR31HG suppressed NPC cell viability and colony formation, promoted apoptosis, and decreased the expressions of p‐PI3K, and p‐AKT. 740Y‐P reversed the above effects of si‐MIR31HG on NPC cells. Besides, MIR31HG expression was positively correlated with AKT1 mRNA expression in HNSC patients.ConclusionMIR31HG silencing promotes NPC cell proliferation and inhibits apoptosis through suppressing the PI3K/AKT signaling pathway.     

Aldosterone alleviates lipopolysaccharide-induced acute lung injury by regulating epithelial sodium channel through PI3K/Akt/SGK1 signaling pathway

Reduced alveolar fluid clearance (AFC) is a major pathological feature of acute lung injury (ALI). Epithelial sodium channel (ENaC) plays a key role in regulating the transport of Na⁺ and clearing alveolar edema fluid effectively. ENaC has been reported to be regulated by aldosterone in the distal collecting tube of the kidney. We hypothesized whether aldosterone regulated ENaC in alveolar epithelium and correspondingly played a role in ALI. In this study we found that the expression of aldosterone synthesis encoding gene, CYP11B2, and ENaC were decreased in the lung tissue of LPS-induced ALI mice. Furthermore, aldosterone alleviated ALI by increasing the expression of ENaC-α and relieving pulmonary edema. Besides, we found that aldosterone upregulated ENaC-α through PI3K/Akt/SGK1 pathway. In conclusion, our study demonstrated that aldosterone attenuated pulmonary edema by upregulating ENaC-α through the PI3K/Akt/SGK1 pathway in LPS-induced ALI, indicating that aldosterone might be a promising adjuvant drug for ALI treatment.     

miR-125b inhibits keratinocyte proliferation and promotes keratinocyte apoptosis in oral lichen planus by targeting MMP-2 expression through PI3 K/Akt/mTOR pathway

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that involves the degeneration of keratinocytes. However, the etiology and mechanisms of OLP pathogenesis have not been fully elucidated. In this study, we used keratinocytes HaCaT stimulated with lipopolysaccharide (LPS) to mimic a local OLP immune environment, and investigated the regulatory role of miR-125b in keratinocyte proliferation and apoptosis under OLP conditions. Immunohistochemical analysis and quantitative real-time PCR (qRT-PCR) assay showed that MMP-2 expression was up-regulated and miR-125b expression was down-regulated in both OLP mucosa tissues and LPS-incubated HaCaT cells. Western blot analysis indicated that miR-125b overexpression suppressed LPS-induced MMP-2 expression in HaCaT cells. Molecularly, our results confirmed that MMP-2 is a target gene of miR-125b in HaCaT cells. The effect of miR-125b on cell proliferation was revealed by CCK-8 assay, BrdU assay and cell cycle analysis, which illustrated that miR-125b overexpression impeded LPS-induced HaCaT cell proliferation. Flow cytometry analysis further demonstrated that miR-125b overexpression promoted HaCaT cell apoptosis. Moreover, these effects were involved in PI3 K/Akt/mTOR activation, as miR-125b overexpression inhibited LPS-enhanced expression of p-Akt and p-mTOR proteins. Taken together, these data confirm that miR-125b might inhibit keratinocyte proliferation and promote keratinocyte apoptosis in OLP pathogenesis by targeting MMP-2 through PI3 K/Akt/mTOR pathway.