Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.
J Clin Lab Anal. 2020 Sep;34(9):e23369. doi: 10.1002/jcla.23369. Epub 2020 Jul 3.
Chemoresistance posed a barrier to successful treatment of breast cancer (BC), and lncRNA MEG3 has been documented to implicate in BC development. However, whether MEG3 methylation, which led to low MEG3 expression, was relevant to BC progression and chemoresistance remained uncertain.
In the aggregate, 374 pairs of tumor tissues and adjacent normal tissues were collected from pathologically confirmed BC patients, and four BC cell lines, including MDA-MB-231, Bcap-37, MCF-7, and SK-BR-3, were purchased. Moreover, methylation-specific polymerase chain reaction (PCR) was adopted to evaluate the methylation status of BC tissues and cell lines, and chemo-tolerance of BC cell lines was assessed by performing MTT assay. Concurrently, transwell assay and scratch assay were carried out to estimate the migratory and invasive capability of BC cell lines.
Methylated MEG3, lowly expressed MEG3, large tumor size (≥2 cm), advanced TNM grade and lymphatic metastasis were potentially symbolic of poor prognosis among BC patients (P < .05). Besides, MDA-MB-231 cell line exhibited the strongest resistance against paclitaxel, adriamycin, and vinorelbine (P < .05), while MCF-7 cell line seemed more sensitive against these drugs than any other BC cell line (P < .05). Furthermore, pcDNA3.1-MEG3 and 5-Aza-dC markedly sensitized MDA-MB-231 and MCF-7 cell lines against the drug treatments (P < .05). Simultaneously, proliferation and metastasis of the BC cell lines were slowed down under the force of pcDNA3.1-MEG3 and 5-Aza-dC (P < .05).
Preventing methylation of MEG3 might matter in lessening BC chemoresistance, owing to its hindering proliferation and metastasis of BC cells.
化疗耐药性是乳腺癌（BC）治疗成功的障碍，已有研究表明长链非编码 RNA MEG3 参与了 BC 的发生发展。然而，导致 MEG3 表达降低的 MEG3 甲基化是否与 BC 进展和化疗耐药相关尚不清楚。
总计收集了 374 对经病理证实的 BC 患者的肿瘤组织和相邻正常组织，并购买了 4 株 BC 细胞系，包括 MDA-MB-231、Bcap-37、MCF-7 和 SK-BR-3。此外，采用甲基化特异性聚合酶链反应（PCR）评估 BC 组织和细胞系的甲基化状态，并通过 MTT 测定评估 BC 细胞系的化疗耐药性。同时，进行 Transwell 测定和划痕测定评估 BC 细胞系的迁移和侵袭能力。
BC 患者中，MEG3 甲基化、MEG3 低表达、肿瘤较大（≥2cm）、TNM 分级较高和淋巴转移与预后不良相关（P<0.05）。此外，MDA-MB-231 细胞系对紫杉醇、阿霉素和长春瑞滨的耐药性最强（P<0.05），而 MCF-7 细胞系对这些药物的敏感性高于其他任何 BC 细胞系（P<0.05）。此外，pcDNA3.1-MEG3 和 5-Aza-dC 显著增强了 MDA-MB-231 和 MCF-7 细胞系对药物治疗的敏感性（P<0.05）。同时，pcDNA3.1-MEG3 和 5-Aza-dC 降低了 BC 细胞系的增殖和迁移（P<0.05）。
抑制 MEG3 甲基化可能有助于减轻 BC 的化疗耐药性，因为它可以抑制 BC 细胞的增殖和转移。
