本文選題：乳腺癌抗雌激素耐藥基因 + 乳腺癌　； 參考：《中國(guó)腫瘤生物治療雜志》2017年07期

【摘要】：目的:探討微小核糖核酸-133(mi R-133)調(diào)控乳腺癌雌激素耐受基因4(breast cancer anti-estrogen resistance 4,BCAR4)對(duì)乳腺癌細(xì)胞遷移和侵襲的影響及其機(jī)制。方法:采集2006年1至12月在鄭州大學(xué)附屬腫瘤醫(yī)院接受手術(shù)切除治療的80例乳腺癌患者的乳腺癌和相應(yīng)癌旁組織。RT-PCR檢測(cè)乳腺癌和癌旁組織BCAR4和mi R-133的表達(dá);雙熒光素酶檢測(cè)BCAR4和mi R-133之間的關(guān)聯(lián);劃痕實(shí)驗(yàn)和Transwell實(shí)驗(yàn)分別檢測(cè)沉默BCAR4或沉默BCAR4和mi R-133后乳腺癌MCF-7細(xì)胞的遷移和侵襲能力;Western blotting檢測(cè)Notch1信號(hào)通路相關(guān)蛋白的表達(dá);裸鼠皮下成瘤實(shí)驗(yàn)檢測(cè)沉默BCAR4對(duì)MCF-7細(xì)胞成瘤能力的影響;生物統(tǒng)計(jì)學(xué)分析BCAR4表達(dá)和乳腺癌患者臨床病理參數(shù)及生存率的關(guān)系。結(jié)果:乳腺癌組織中BCAR4表達(dá)顯著高于癌旁組織(P0.05);雙熒光素酶實(shí)驗(yàn)顯示BCAR4可以調(diào)控mi R-133的表達(dá);沉默BCAR4表達(dá)可以抑制乳腺癌MCF-7細(xì)胞的遷移和侵襲;沉默mi R-133和BCAR4表達(dá)的MCF-7細(xì)胞的遷移率和穿膜細(xì)胞數(shù)顯著高于僅沉默BCAR4表達(dá)的MCF-7細(xì)胞[遷移率(92.31±8.64)%vs(52.61±5.12)%,P0.05;穿膜細(xì)胞數(shù):(171.38±12.61)vs(28.54±3.29),P0.01],抑制mi R-133可以逆轉(zhuǎn)BCAR4抑制乳腺癌MCF-7細(xì)胞遷移、侵襲能力;沉默BCAR4組裸鼠成瘤的體積和質(zhì)量都顯著減小;沉默BCAR4的MCF-7細(xì)胞的Notch1通路相關(guān)蛋白表達(dá)水平明顯下調(diào);BCAR4表達(dá)與乳腺癌的病理分期及淋巴結(jié)轉(zhuǎn)移顯著相關(guān),BCAR4高表達(dá)患者生存率較BCAR4低表達(dá)患者低。結(jié)論:乳腺癌MCF-7細(xì)胞的侵襲和遷移受到BCAR4和mi R-133的雙重調(diào)控,mi R-133可能通過Notch1信號(hào)通路調(diào)節(jié)BCAR4對(duì)乳腺癌細(xì)胞遷移和侵襲的影響,可為乳腺癌分子靶向治療及乳腺癌耐藥機(jī)制的研究提供思路。
[Abstract]:Aim: to investigate the effects of small ribonucleic acid (RNC-133mR-133) on the migration and invasion of breast cancer cells regulated by the estrogen tolerance gene 4(breast cancer anti-estrogen resistance 4 (BCAR4) and its mechanism. Methods: the expressions of BCAR4 and miR-133 in breast cancer and adjacent tissues were detected by RT-PCR in 80 patients with breast cancer treated by surgical excision from January to December 2006 in the affiliated Cancer Hospital of Zhengzhou University. The relationship between BCAR4 and miR-133 was detected by double luciferase assay, the migration and invasion ability of breast cancer MCF-7 cells after silencing BCAR4 or silencing BCAR4 and miR-133 was detected by scratch test and Transwell assay respectively. Western blotting was used to detect the expression of Notch1 signal pathway related protein. The effect of silencing BCAR4 on the tumorigenesis of MCF-7 cells was detected by subcutaneous tumorigenesis assay in nude mice, and the relationship between BCAR4 expression and clinicopathological parameters and survival rate of breast cancer patients was analyzed by biostatistics. Results: the expression of BCAR4 in breast cancer tissues was significantly higher than that in adjacent tissues (P 0.05), double luciferase assay showed that BCAR4 could regulate the expression of miR-133, and silencing BCAR4 expression could inhibit the migration and invasion of breast cancer MCF-7 cells. The migration rate and the number of perforating cells of MCF-7 cells silencing the expression of miR-133 and BCAR4 were significantly higher than those of MCF-7 cells only silencing the expression of BCAR4 [migration rate was 92.31 鹵8.64)%vs(52.61 鹵5.12], and the number of transmembrane cells was 171.38 鹵12.61)vs(28.54 鹵3.29P0.01, and the inhibition of MIR-133 could reverse the ability of BCAR4 to inhibit the migration and invasion of MCF-7 cells of breast cancer. In silencing BCAR4 group, the tumor size and mass of nude mice decreased significantly. The expression level of Notch1 pathway related protein in MCF-7 cells silenced by BCAR4 was significantly lower than that in patients with low expression of BCAR4, and the expression of BCAR4 was significantly correlated with the pathological stage and lymph node metastasis of breast cancer. The survival rate of patients with high expression of BCAR4 was significantly lower than that of patients with low expression of BCAR4. Conclusion: the invasion and migration of breast cancer MCF-7 cells are regulated by BCAR4 and miR-133, which may regulate the effect of BCAR4 on the migration and invasion of breast cancer cells through Notch1 signaling pathway. It can provide ideas for molecular targeted therapy of breast cancer and the mechanism of drug resistance in breast cancer.
【作者單位】： 鄭州大學(xué)附屬腫瘤醫(yī)院病理科;
【基金】：河南省基礎(chǔ)與前沿技術(shù)研究計(jì)劃基金資助項(xiàng)目(No.102300410038)~~
【分類號(hào)】：R737.9

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