miRNA-21调节抑癌基因PTEN参与卵巢癌发病的机制研究
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摘要
[研究背景]
卵巢癌是妇科常见的三大恶性肿瘤之一,早期病情隐匿,诊断困难,多数患者就诊时已属晚期,死亡率居妇科恶性肿瘤首位。卵巢癌细胞具有较强的恶性生物学行为,易出现盆腹腔内广泛的种植转移,然而对卵巢癌的发病及恶性生物学行为机制尚不明确。因此揭示卵巢癌的发生发展机制,寻找新的诊断及治疗靶点,是目前亟待解决的任务。
MicroRNAs(miRNAs)是一种长约22nt的单链小分子RNA。广泛存在于真核生物中,是一组不编码蛋白质的短序列RNA,可通过与mRNA分子序列互补相结合,参与基因转录后水平调控,呈现出组织特异性或发育阶段特异性表达特征。近年来,随着生物信息学的迅猛发展和研究手段的进步,越来越多miRNAs分子在各种生物中不断被揭示,目前已有700多个miRNAs被发现,调控机体内1/3以上基因表达,参与生命过程中一系列的重要进程,包括胚胎发育、干细胞分化、细胞增殖与凋亡,造血生成及激素分泌等多种生物学过程。越来越多的证据表明,miRNAs参与癌症的发生。研究发现,在多种肿瘤组织及细胞系中检测到miRNAs的异常表达,50%以上的miRNA基因位于肿瘤相关的基因组区域或脆性位点,可能通过调节体内某些抑癌基因或癌基因的表达,在肿瘤的发生发展中发挥重要致癌或抑癌的功能。
有研究报道,miR-21通过调节PTEN、PDCD4、TPM-Ⅰ及TIMPs等抑癌基因的表达,促进细胞增殖和抑制凋亡。已发现其在乳腺癌、胶质母细胞瘤、胃癌、肺癌、肝癌等多种癌组织中过高表达,是实体肿瘤中最常见的高表达miRNAs之一,在肿瘤的发生发展中可能起到一个癌基因的作用。目前,已相继有研究证实,在卵巢癌组织、病人血清及外周血小体中检测到多种miRNAs的异常表达,其中miR-21不仅在卵巢癌组织中过高表达,而且在病人血清及外周血小体中也同样检测到miR-21的异常表达,提示miR-21在卵巢癌的发生发展中可能具有不容忽视的重要地位。但有关miR-21在卵巢癌发生发展中的功能及作用机制国内外尚未见报道。
本研究目的是检测miR-21及PTEN在上皮性卵巢癌中的表达,并通过RNA干扰技术抑制卵巢癌细胞系中miR-21的表达,观察miR-21对PTEN的影响及miR-21对细胞增殖、迁移及侵袭能力的调控作用。探讨miR-21在卵巢癌发生发展、侵袭转移等过程中的作用机制,为寻找卵巢癌的诊断及治疗新靶点提供理论依据。
目的：检测上皮性卵巢癌组织中miR-21及PTEN蛋白的表达,分析miR-21异常表达与PTEN蛋白的相关性及其与卵巢癌临床分期、组织分级、病理类型等特征间的关系,初步探讨miR-21及PTEN在卵巢癌分子发病中的作用。
方法：采用茎环实时荧光逆转录聚合酶链反应(stem-loop real-time RT-PCR)检测上皮性卵巢癌组织、良性上皮性卵巢肿瘤及正常卵巢组织标本中miR-21表达。采用链霉菌抗生物素蛋白-过氧化酶(SP)免疫组化方法检测上述组织中PTEN蛋白表达。
结果：1.miR-21在卵巢癌组织中的相对表达量(2-△△CT)为4.849±1.813,显著高于良性卵巢肿瘤(1.133±0.291)及正常卵巢组织(P<0.01),在良性卵巢肿瘤和正常卵巢组织间miR-21表达量无明显差异。
2.miR-21在Ⅲ、Ⅳ期卵巢癌组织中表达量为5.603±1.787,明显高于其在Ⅰ、Ⅱ期组织中表达3.341±0.254(p<0.01)；在低分化卵巢癌组织中表达量为7.057±1.552,明显高于其在中高分化癌组织中表达3.845±0.680(p<0.01)；在淋巴结转移组表达量为7.095±1.728,明显高于无淋巴结转移组4.100±1.070(p<0.01);miR-21在浆液性、粘液性及内膜样卵巢癌组织中的相对表达量无明显差异。
3. PTEN在卵巢癌组织中阳性表达率为41.66%,明显低于卵巢良性肿瘤(83.33%)及正常卵巢(100%)；在Ⅲ、Ⅳ卵巢癌组织中PTEN阳性表达率明显低于Ⅰ、Ⅲ期(25%vs 75%,P=0.001)；在低分化卵巢癌组织中阳性表达率明显低于中高分化(10.71%vs85%,P=0.000)；在淋巴结转移组.PTEN阳性表达率为16.66%,明显低于无转移组50.00%(P=0.034)。miR-21及PTEN均与组织病理类型无关。
4.相关分析结果表明,卵巢癌组织中miR-21表达量与PTEN阳性表达率存在显著负相关(r=-0.447,P<0.01)；
结论：miR-21在上皮性卵巢癌组织中高表达,且与卵巢癌分期、组织分级及淋巴结转移密切相关,在卵巢癌发生发展中发挥重要的癌基因作用。miR-21与PTEN蛋白表达呈负相关,二者可能共同参与卵巢癌的发病机制。
目的：拟通过siRNA干扰卵巢癌细胞系中miR-21的表达,分析降调miR-21的表达后对卵巢癌细胞中PTEN蛋白表达及细胞的增殖、迁移及侵袭能力的影响,进一步揭示miR-21在卵巢癌分子发病中的作用机制。
方法：选用卵巢癌细胞系OVCAR3进行体外培养,采用shRNA表达载体法,根据miR-21的两个成熟片段,设计合成干扰miR-21的siRNA序列,并与表达载体pSIREN-RetroQ连接重组,合成质粒pSIREN-miR-21-1、pSIREN-miR-21-2及pSIREN-miR-21-Neg,分别转染卵巢癌OVCAR3细胞系,干扰miR-21在OVCAR3中的表达,同时设立空白对照组。采用茎环实时荧光逆转录聚合酶链反应(stem-loop real-time RT-PCR)检测转染后细胞系中miR-21表达。Western blot方法检测转染后细胞系中PTEN蛋白表达,应用MTT实验、划痕实验和Transwell细胞侵袭实验方法分析转染后细胞增殖、迁移及侵袭能力的变化。探讨miR-21在卵巢癌发生发展中的可能作用机制。
结果：1. Real time RCR结果显示pSIREN-miR-21-1和pSIREN-miR-21-2转染组细胞中miR-21相对表达量(2-△△CT)为0.26±0.08、0.19±0.06,明显低于阴性对照(1.26±0.21)及空白对照组(1.0±0.19),说明两组干扰质粒均具有良好的干扰效果。转染72小时后,Western blot检测PTEN在pSIREN-miR-21-1和pSIREN-miR-21-2组中表达明显上调,pSIREN-miR-21-neg组无明显变化。
2.MTT检测转染后细胞增殖活力,显示在转染pSIREN-miR-21-1和pSIREN-miR-21-2组中,OVCAR3细胞增殖的抑制率分别为23.9%和29.4%,均明显高于对照组(p<0.05,p<0.01),说明肿瘤细胞增殖能力的下降。
4.划痕实验结果显示：经过48小时无血清培养后,空白对照组和转染pSIREN-miR-21-neg组中的划痕已经基本长满细胞,而pSIREN-miR-21-1组中有少量细胞,但仍可见明显划痕。pSIREN-miR-21-2组愈合最差,划痕中央无细胞。提示转染pSIREN-miR-21-1和-2组中细胞的活能力受到明显的抑制。
5. Transwell实验：转染pSIREN-miR-21-1和pSIREN-miR-21-2组中24小时内穿透小室聚碳酸酯膜的细胞数为40±3.56和29.5±2.38,明显低于空白对照组(73±2.16)和阴性对照组为(69±1.83),卵巢癌细胞在转染pSIREN-miR-21质粒后,侵袭能力也明显下降。
结论：干扰质粒pSIREN-miR-21能够成功抑制卵巢癌细胞系中miR-21表达,直接导致PTEN蛋白表达增加,进而对卵巢癌细胞的增殖、侵袭及迁移能力产生抑制。说明miR-21通过PTEN调控卵巢癌细胞的恶性生物学行为,是导致卵巢癌发生发展及浸润转移的重要调节机制。
Objective:To investigate the expression of miR-21 and PTEN in epithelial ovarian cancers (EOC) and their correlation with the clinicopathologic features of the patients.
Methods:Stem-loop real-time RT-PCR was used to detect the expression of miR-21 in epithelial ovarian cancers and benign epithelial ovarian cysts and normal ovarian tissues. PTEN protein was also examined with S-P immunohistochemistry method. Their correlation with histological differentiation, clinicopathological stage, and lymph node status was analyzed.
Results:Among the 48 ovarian cancer samples analyzed, the relative expression of miR-21 (2-△△CT= 4.849±1.813) was significantly upregulated by 4-fold or more compared with the benign ovarian cysts (2-△△CT=1.133±0.291) and normal ovarian tissues (2-△△CT=1.057±0.126) (P＜0.01, respectively). No differences were observed in miR-21 relative expression between benign ovarian cysts and normal controls. The relative expressions of miR-21 were significantly higher in advanced stage and grade 3 tumor samples compared to the early stage and grade 1 to 2 tumor samples (2-△△CT=5.603±1.787 vs.3.341±0.254 and 2-△△CT=7.057±1.552 vs.3.845±0.680, p＜0.01 respectively). The same differences were observed between the lymph node positive group and negative group (2-△△CT= 7.095±1.728 vs.4.100±1.070, p＜0.01).
20 of 48 (41.66%) ovarian cancer tissues were positive for PTEN, mainly weakly positive and expressed in the cytoplasm, which was distinctly lower than that in begin ovarian cysts and normal controls. Moreover, eight of 32 (25%) stageⅢ-Ⅳtissue samples were positive for PTEN, which was lower than that in stageⅠ-Ⅱtissue samples (12/16,75%). Three of 28 (10.71%) grade 3 tissue samples and two of 12 (16.66%) lymph node positive samples were positive for PTEN, which are obviously lower compared with gradel-2 samples (17/20,85%) and lymph node negative samples (18/36,50%) Both miR-21 and PTEN have no correlation with distinct histotypes of ovarian cancers.
Seven cases were positive for PTEN among the 21 cases of ovarian cancer tissues with relatively low miR-21 expression (3.410±0.261), but only six cases were positive for PTEN among the 27 cases of ovarian cancer tissues with relatively high miR-21 expression (5.967±1.711). Spearman rank correlation analysis showed that PTEN expression was negatively correlated with miR-21 expression (r=-0.447, P＜0.01)
Conclusion:Our data suggest that miR-21 aberrantly expressed in EOC and negtively correlated with PTEN, it might play an important role as an oncogene in the genesis and development of epithelial ovarian cancer.
Objective:To detect the expression of PTEN and changes in cell proliferation, migration and invasion capabilities after downregulating the miR-21 expression in OVCAR3 cells with siRNA method. And investigate the mechanism by which miR-21 negatively controls the expression of PTEN, might play an important role as an oncogene, in the genesis and development of epithelial ovarian cancer.
Methods:A short-hairpin RNA specifically targeting miR-21 was constructed and ligated with vector Linear pSIREN-RetroQ, resulting in three recombinants: pSIREN-miR-21-1、pSIREN-miR-21-2 and pSIREN-miR-21-Neg which were used to transfected OVCAR3 cells respectively. Stem-loop real-time RT-PCR was used to detect the expression of miR-21 and western blotting for PTEN protein. Cell proliferation, invasion and migration abilities were examined using MTT assay, Scratch-wound assay and transwell invasion assay respectively.
Results:Seventy-two hours after infection, the infection efficiency reached more than 70% in the three groups of infected cells indicating successful transfection in all groups. miR-21 expression levels decreased and PTEN increased significantly both in pSIREN-miR-21-1 and pSIREN-miR-21-2 infected cells compared to pSIREN-miR-21-Neg infected cells and control group, that indicate inhibition of miR-21 can significantly increased PTEN expression in OVCAR3 cell lines. MTT assay indicates transfection of miR-21 inhibitor(pSIREN-miR-21-1 and-2) resulted in significant inhibition of 23.9% and 29.4% respectively at 72 hours in OVCAR3 cells indicating cell proliferation ability was decreased. Scratch-wound assay indicated cells migrated slowly after transfected with pSIREN-miR-21-1 and-2 compared with the control. Transwell invasion assay indicated the number of invasive cells in pSIREN-miR-21-1 group and group 2 was 40±3.56 and 29.5±2.38 that was significantly reduced relative to the control cells and pSIREN-miR-21-neg group (73±1.26,69±1.83).
Conclusion:Our data suggest that the relative expression of miR-21 could be inhibited successfully using RNA interference. The downregulation of miR-21 could inhibite the cell proliferation, invasion and migration abilities through increasing the expression of PTEN protein in OVCAR3 cells that might play an important role in the genesis and development of epithelial ovarian cancer.
卵巢癌是妇科常见的三大恶性肿瘤之一,早期病情隐匿,诊断困难,多数患者就诊时已属晚期,死亡率居妇科恶性肿瘤首位。卵巢癌细胞具有较强的恶性生物学行为,易出现盆腹腔内广泛的种植转移,然而对卵巢癌的发病及恶性生物学行为机制尚不明确。因此揭示卵巢癌的发生发展机制,寻找新的诊断及治疗靶点,是目前亟待解决的任务。
MicroRNAs(miRNAs)是一种长约22nt的单链小分子RNA。广泛存在于真核生物中,是一组不编码蛋白质的短序列RNA,可通过与mRNA分子序列互补相结合,参与基因转录后水平调控,呈现出组织特异性或发育阶段特异性表达特征。近年来,随着生物信息学的迅猛发展和研究手段的进步,越来越多miRNAs分子在各种生物中不断被揭示,目前已有700多个miRNAs被发现,调控机体内1/3以上基因表达,参与生命过程中一系列的重要进程,包括胚胎发育、干细胞分化、细胞增殖与凋亡,造血生成及激素分泌等多种生物学过程。越来越多的证据表明,miRNAs参与癌症的发生。研究发现,在多种肿瘤组织及细胞系中检测到miRNAs的异常表达,50%以上的miRNA基因位于肿瘤相关的基因组区域或脆性位点,可能通过调节体内某些抑癌基因或癌基因的表达,在肿瘤的发生发展中发挥重要致癌或抑癌的功能。
有研究报道,miR-21通过调节PTEN、PDCD4、TPM-Ⅰ及TIMPs等抑癌基因的表达,促进细胞增殖和抑制凋亡。已发现其在乳腺癌、胶质母细胞瘤、胃癌、肺癌、肝癌等多种癌组织中过高表达,是实体肿瘤中最常见的高表达miRNAs之一,在肿瘤的发生发展中可能起到一个癌基因的作用。目前,已相继有研究证实,在卵巢癌组织、病人血清及外周血小体中检测到多种miRNAs的异常表达,其中miR-21不仅在卵巢癌组织中过高表达,而且在病人血清及外周血小体中也同样检测到miR-21的异常表达,提示miR-21在卵巢癌的发生发展中可能具有不容忽视的重要地位。但有关miR-21在卵巢癌发生发展中的功能及作用机制国内外尚未见报道。
本研究目的是检测miR-21及PTEN在上皮性卵巢癌中的表达,并通过RNA干扰技术抑制卵巢癌细胞系中miR-21的表达,观察miR-21对PTEN的影响及miR-21对细胞增殖、迁移及侵袭能力的调控作用。探讨miR-21在卵巢癌发生发展、侵袭转移等过程中的作用机制,为寻找卵巢癌的诊断及治疗新靶点提供理论依据。
目的：检测上皮性卵巢癌组织中miR-21及PTEN蛋白的表达,分析miR-21异常表达与PTEN蛋白的相关性及其与卵巢癌临床分期、组织分级、病理类型等特征间的关系,初步探讨miR-21及PTEN在卵巢癌分子发病中的作用。
方法：采用茎环实时荧光逆转录聚合酶链反应(stem-loop real-time RT-PCR)检测上皮性卵巢癌组织、良性上皮性卵巢肿瘤及正常卵巢组织标本中miR-21表达。采用链霉菌抗生物素蛋白-过氧化酶(SP)免疫组化方法检测上述组织中PTEN蛋白表达。
结果：1.miR-21在卵巢癌组织中的相对表达量(2-△△CT)为4.849±1.813,显著高于良性卵巢肿瘤(1.133±0.291)及正常卵巢组织(P<0.01),在良性卵巢肿瘤和正常卵巢组织间miR-21表达量无明显差异。
2.miR-21在Ⅲ、Ⅳ期卵巢癌组织中表达量为5.603±1.787,明显高于其在Ⅰ、Ⅱ期组织中表达3.341±0.254(p<0.01)；在低分化卵巢癌组织中表达量为7.057±1.552,明显高于其在中高分化癌组织中表达3.845±0.680(p<0.01)；在淋巴结转移组表达量为7.095±1.728,明显高于无淋巴结转移组4.100±1.070(p<0.01);miR-21在浆液性、粘液性及内膜样卵巢癌组织中的相对表达量无明显差异。
3. PTEN在卵巢癌组织中阳性表达率为41.66%,明显低于卵巢良性肿瘤(83.33%)及正常卵巢(100%)；在Ⅲ、Ⅳ卵巢癌组织中PTEN阳性表达率明显低于Ⅰ、Ⅲ期(25%vs 75%,P=0.001)；在低分化卵巢癌组织中阳性表达率明显低于中高分化(10.71%vs85%,P=0.000)；在淋巴结转移组.PTEN阳性表达率为16.66%,明显低于无转移组50.00%(P=0.034)。miR-21及PTEN均与组织病理类型无关。
4.相关分析结果表明,卵巢癌组织中miR-21表达量与PTEN阳性表达率存在显著负相关(r=-0.447,P<0.01)；
结论：miR-21在上皮性卵巢癌组织中高表达,且与卵巢癌分期、组织分级及淋巴结转移密切相关,在卵巢癌发生发展中发挥重要的癌基因作用。miR-21与PTEN蛋白表达呈负相关,二者可能共同参与卵巢癌的发病机制。
目的：拟通过siRNA干扰卵巢癌细胞系中miR-21的表达,分析降调miR-21的表达后对卵巢癌细胞中PTEN蛋白表达及细胞的增殖、迁移及侵袭能力的影响,进一步揭示miR-21在卵巢癌分子发病中的作用机制。
方法：选用卵巢癌细胞系OVCAR3进行体外培养,采用shRNA表达载体法,根据miR-21的两个成熟片段,设计合成干扰miR-21的siRNA序列,并与表达载体pSIREN-RetroQ连接重组,合成质粒pSIREN-miR-21-1、pSIREN-miR-21-2及pSIREN-miR-21-Neg,分别转染卵巢癌OVCAR3细胞系,干扰miR-21在OVCAR3中的表达,同时设立空白对照组。采用茎环实时荧光逆转录聚合酶链反应(stem-loop real-time RT-PCR)检测转染后细胞系中miR-21表达。Western blot方法检测转染后细胞系中PTEN蛋白表达,应用MTT实验、划痕实验和Transwell细胞侵袭实验方法分析转染后细胞增殖、迁移及侵袭能力的变化。探讨miR-21在卵巢癌发生发展中的可能作用机制。
结果：1. Real time RCR结果显示pSIREN-miR-21-1和pSIREN-miR-21-2转染组细胞中miR-21相对表达量(2-△△CT)为0.26±0.08、0.19±0.06,明显低于阴性对照(1.26±0.21)及空白对照组(1.0±0.19),说明两组干扰质粒均具有良好的干扰效果。转染72小时后,Western blot检测PTEN在pSIREN-miR-21-1和pSIREN-miR-21-2组中表达明显上调,pSIREN-miR-21-neg组无明显变化。
2.MTT检测转染后细胞增殖活力,显示在转染pSIREN-miR-21-1和pSIREN-miR-21-2组中,OVCAR3细胞增殖的抑制率分别为23.9%和29.4%,均明显高于对照组(p<0.05,p<0.01),说明肿瘤细胞增殖能力的下降。
4.划痕实验结果显示：经过48小时无血清培养后,空白对照组和转染pSIREN-miR-21-neg组中的划痕已经基本长满细胞,而pSIREN-miR-21-1组中有少量细胞,但仍可见明显划痕。pSIREN-miR-21-2组愈合最差,划痕中央无细胞。提示转染pSIREN-miR-21-1和-2组中细胞的活能力受到明显的抑制。
5. Transwell实验：转染pSIREN-miR-21-1和pSIREN-miR-21-2组中24小时内穿透小室聚碳酸酯膜的细胞数为40±3.56和29.5±2.38,明显低于空白对照组(73±2.16)和阴性对照组为(69±1.83),卵巢癌细胞在转染pSIREN-miR-21质粒后,侵袭能力也明显下降。
结论：干扰质粒pSIREN-miR-21能够成功抑制卵巢癌细胞系中miR-21表达,直接导致PTEN蛋白表达增加,进而对卵巢癌细胞的增殖、侵袭及迁移能力产生抑制。说明miR-21通过PTEN调控卵巢癌细胞的恶性生物学行为,是导致卵巢癌发生发展及浸润转移的重要调节机制。
Objective:To investigate the expression of miR-21 and PTEN in epithelial ovarian cancers (EOC) and their correlation with the clinicopathologic features of the patients.
Methods:Stem-loop real-time RT-PCR was used to detect the expression of miR-21 in epithelial ovarian cancers and benign epithelial ovarian cysts and normal ovarian tissues. PTEN protein was also examined with S-P immunohistochemistry method. Their correlation with histological differentiation, clinicopathological stage, and lymph node status was analyzed.
Results:Among the 48 ovarian cancer samples analyzed, the relative expression of miR-21 (2-△△CT= 4.849±1.813) was significantly upregulated by 4-fold or more compared with the benign ovarian cysts (2-△△CT=1.133±0.291) and normal ovarian tissues (2-△△CT=1.057±0.126) (P＜0.01, respectively). No differences were observed in miR-21 relative expression between benign ovarian cysts and normal controls. The relative expressions of miR-21 were significantly higher in advanced stage and grade 3 tumor samples compared to the early stage and grade 1 to 2 tumor samples (2-△△CT=5.603±1.787 vs.3.341±0.254 and 2-△△CT=7.057±1.552 vs.3.845±0.680, p＜0.01 respectively). The same differences were observed between the lymph node positive group and negative group (2-△△CT= 7.095±1.728 vs.4.100±1.070, p＜0.01).
20 of 48 (41.66%) ovarian cancer tissues were positive for PTEN, mainly weakly positive and expressed in the cytoplasm, which was distinctly lower than that in begin ovarian cysts and normal controls. Moreover, eight of 32 (25%) stageⅢ-Ⅳtissue samples were positive for PTEN, which was lower than that in stageⅠ-Ⅱtissue samples (12/16,75%). Three of 28 (10.71%) grade 3 tissue samples and two of 12 (16.66%) lymph node positive samples were positive for PTEN, which are obviously lower compared with gradel-2 samples (17/20,85%) and lymph node negative samples (18/36,50%) Both miR-21 and PTEN have no correlation with distinct histotypes of ovarian cancers.
Seven cases were positive for PTEN among the 21 cases of ovarian cancer tissues with relatively low miR-21 expression (3.410±0.261), but only six cases were positive for PTEN among the 27 cases of ovarian cancer tissues with relatively high miR-21 expression (5.967±1.711). Spearman rank correlation analysis showed that PTEN expression was negatively correlated with miR-21 expression (r=-0.447, P＜0.01)
Conclusion:Our data suggest that miR-21 aberrantly expressed in EOC and negtively correlated with PTEN, it might play an important role as an oncogene in the genesis and development of epithelial ovarian cancer.
Objective:To detect the expression of PTEN and changes in cell proliferation, migration and invasion capabilities after downregulating the miR-21 expression in OVCAR3 cells with siRNA method. And investigate the mechanism by which miR-21 negatively controls the expression of PTEN, might play an important role as an oncogene, in the genesis and development of epithelial ovarian cancer.
Methods:A short-hairpin RNA specifically targeting miR-21 was constructed and ligated with vector Linear pSIREN-RetroQ, resulting in three recombinants: pSIREN-miR-21-1、pSIREN-miR-21-2 and pSIREN-miR-21-Neg which were used to transfected OVCAR3 cells respectively. Stem-loop real-time RT-PCR was used to detect the expression of miR-21 and western blotting for PTEN protein. Cell proliferation, invasion and migration abilities were examined using MTT assay, Scratch-wound assay and transwell invasion assay respectively.
Results:Seventy-two hours after infection, the infection efficiency reached more than 70% in the three groups of infected cells indicating successful transfection in all groups. miR-21 expression levels decreased and PTEN increased significantly both in pSIREN-miR-21-1 and pSIREN-miR-21-2 infected cells compared to pSIREN-miR-21-Neg infected cells and control group, that indicate inhibition of miR-21 can significantly increased PTEN expression in OVCAR3 cell lines. MTT assay indicates transfection of miR-21 inhibitor(pSIREN-miR-21-1 and-2) resulted in significant inhibition of 23.9% and 29.4% respectively at 72 hours in OVCAR3 cells indicating cell proliferation ability was decreased. Scratch-wound assay indicated cells migrated slowly after transfected with pSIREN-miR-21-1 and-2 compared with the control. Transwell invasion assay indicated the number of invasive cells in pSIREN-miR-21-1 group and group 2 was 40±3.56 and 29.5±2.38 that was significantly reduced relative to the control cells and pSIREN-miR-21-neg group (73±1.26,69±1.83).
Conclusion:Our data suggest that the relative expression of miR-21 could be inhibited successfully using RNA interference. The downregulation of miR-21 could inhibite the cell proliferation, invasion and migration abilities through increasing the expression of PTEN protein in OVCAR3 cells that might play an important role in the genesis and development of epithelial ovarian cancer.
引文
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