circ_0000144在乳腺癌中的表达及其对乳腺癌细胞增殖、迁移和侵袭能力的影响

doi:10.6040/j.issn.1671-7554.0.2024.0570

摘要/Abstract

摘要： 目的探究circ_0000144在乳腺癌组织中的表达及其对乳腺癌细胞增殖、凋亡、迁移和侵袭能力的影响。方法通过实时荧光定量PCR(quantitative real-time polymerase chain reaction, RT-qPCR)实验检测49例乳腺癌及配对癌旁正常乳腺组织标本中的circ_0000144表达水平,并分析circ_0000144的表达水平与乳腺癌患者临床病理特征的关系;以正常乳腺上皮细胞MCF-10A为对照,RT-qPCR法检测乳腺癌细胞系(T47D、MCF-7、MDA-MB-231)中circ_0000144表达;以MCF-7细胞为研究对象,将转染si-circ_0000144组设为实验组(si-circ_0000144组),将转染si-NC组设为生理盐水对照组(si-NC组),同时设置空白对照组(Control组),细胞不进行任何转染操作,用常规培养基进行培养,通过CCK-8、克隆形成实验、流式细胞术、划痕实验、Transwell实验检测乳腺癌细胞中细胞增殖、迁移和侵袭的能力,Western blotting法检测相关蛋白CyclinD1、p21、Bax、Bcl-2、E-cadherin和N-cadherin表达。结果与癌旁正常组织比较,乳腺癌组织中circ_0000144表达显著升高(P<0.001),且与TNM分期和淋巴结转移呈密切正相关(P=0.003,P=0.007);与正常乳腺上皮细胞MCF-10A比较,乳腺癌细胞系中circ_0000144表达上调(P<0.001);与Control组或si-NC组比较,si-circ_0000144组增殖、迁移和侵袭能力降低(P均<0.001),凋亡率升高(P均<0.001),CyclinD1、Bcl-2和N-cadherin蛋白表达水平降低(P均<0.001),而p21、Bax和E-cadherin蛋白表达水平升高(P均<0.001)。结论 circ_0000144在乳腺癌组织及细胞系中呈高表达,下调circ_0000144可阻碍乳腺癌细胞增殖、迁移和侵袭,而促进其凋亡,circ_0000144有望成为治疗乳腺癌的分子靶点。

关键词: 乳腺癌, circ_0000144, 增殖, 凋亡, 迁移, 侵袭

Abstract: Objective To explore the expression of circ_0000144 in breast cancer tissues and its effect on the proliferation, apoptosis, migration and invasion abilities of breast cancer cells. Methods Quantitative real-time polymerase chain reaction(RT-qPCR)experiments were performed to detect the expression level of circ_0000144 in 49 breast cancer tissues and paired paracancerous normal breast tissue specimens and to analyze the relationship between the expression level of circ_0000144 and the clinicopathological characteristics of breast cancer patients. Normal breast epithelial cells MCF-10A were used as the control, and circ_0000144 expression was detected in breast cancer cell lines(T47D, MCF-7, MDA-MB-231)by RT-qPCR. MCF-7 cells were used as the study object, and the transfected si-circ_0000144 group was set up as the experimental group(si-circ_0000144 group), the transfected si-NC group was set as the saline control group(si-NC group), and a blank control group(Control group)was set at the same time. The cells were cultured with conventional medium without any transfection operation. The abilities of cell proliferation, migration and invasion in breast cancer cells were detected by CCK-8, clone formation assay, flow cytometry, scratch assay and Transwell assay, and the protein expressions of CyclinD1, p21, Bax, Bcl-2, E-cadherin and N-cadherin were detected by Western blotting. Results The expression of circ_0000144 in breast cancer tissues was significantly elevated compared with that in normal tissues adjacent to the cancer(P<0.001), and was closely positively associated with TNM stage and lymph node metastasis(P=0.003, P=0.007). The expressions of circ_0000144 were up-regulated in breast cancer cell lines compared to normal breast epithelial cells MCF-10A(P<0.001). Compared with the Control group or si-NC group, the si-Circ_0000144 group showed reduced abilities of proliferate, migrate and invade(all P<0.001), elevated apoptosis rate(both P<0.001), decreased expression levels of CyclinD1, Bcl-2 and N-cadherin proteins(all P<0.001), and increased expression levels of p21, Bax and E-cadherin proteins(all P<0.001). Conclusion circ_0000144 is highly expressed in breast cancer tissues and cell lines. Down-regulation of circ_0000144 can hinder breast cancer cell proliferation, migration and invasion, and promote its apoptosis. circ_0000144 may become a molecular target for breast cancer treatment.

Key words: Breast cancer, circ_0000144, Proliferation, Apoptosis, Migration, Invasion

中图分类号:

R730

张洁,张芳芳,王靖楠,李泽宇,宋颖,李娜. circ_0000144在乳腺癌中的表达及其对乳腺癌细胞增殖、迁移和侵袭能力的影响[J]. 山东大学学报 (医学版), 2025, 63(1): 35-42.

ZHANG Jie, ZHANG Fangfang, WANG Jingnan, LI Zeyu, SONG Ying, LI Na. Expression of circ_0000144 in breast cancer and its effect on the proliferation, migration and invasion ability of breast cancer cells[J]. Journal of Shandong University (Health Sciences), 2025, 63(1): 35-42.

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