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Hypermethylation of lncRNA MEG3 impairs chemosensitivity of breast cancer cells.

ABSTRACT: BACKGROUND: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. METHODS: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. RESULTS: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). CONCLUSION:Preventing methylation of MEG3 might matter in lessening BC chemoresistance, owing to its hindering proliferation and metastasis of BC cells.

SUBMITTER: Li H

PROVIDER: S-EPMC7521317 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Hypermethylation of lncRNA MEG3 impairs chemosensitivity of breast cancer cells.

Li Hongchang H Wang Puhua P Liu Jiazhe J Liu Weiyan W Wu Xubo X Ding Junbin J Kang Jie J Li Jindong J Lu Jingfeng J Pan Gaofeng G

Journal of clinical laboratory analysis 20200703 9

<h4>Background</h4>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.<h4>Methods</h4>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, Bc ...[more]

PMID: 32618397

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Project description:BackgroundBreast cancer is the most common malignancy in women, and neoadjuvant chemotherapy has been recommended to the patients with locally advanced breast cancer as the initial treatments. Long non-coding RNA (lncRNA) MEG3, an identified tumor suppressor, has been implicated in the development of various cancers. However, there is no data to evaluate the effect of MEG3 polymorphisms on neoadjuvant treatment in the breast cancer.MethodsGenotyping was performed using Nanodispenser Spectro CHIP chip spotting and Mass ARRAY Compact System. Univariate and multivariate logistic regression analyses were used to analyze the associations between the MEG3 polymorphisms and the pathological complete response (pCR). The disease-free survival (DFS) was estimated by the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to calculate the hazard ratios (HRs) with a 95% confidential interval (CI).ResultsA total of 144 patients with available pretreatment blood species were enrolled in the SHPD002 clinic trial of neoadjuvant chemotherapy for breast cancer. MEG3 rs10132552 were significantly associated with good response (Adjusted OR = 2.79, 95% CI 1.096-7.103, p = 0.031) in dominant model. Median follow-up time was 20 months. In multiple regression analysis, rs10132552 TC + CC (adjusted HR = 0.127, 95% CI 0.22-0.728, p = 0.02) and rs941576 AG + GG (adjusted HR = 0.183, 95% CI 0.041-0.807, p = 0.025) were significantly associated with good DFS. MEG3 rs7158663 (OR = 0.377, 95% CI 0.155-0.917, p = 0.032) were associated with a low risk of hemoglobin decrease in dominant models.ConclusionsLncRNA MEG3 polymorphisms were associated with the chemotherapy response and toxicity of paclitaxel and cisplatin. The result indicates that MEG3 polymorphisms can be considered as the predictive and prognostic markers for the breast cancer patients.Trial registrationRetrospectively registered (ClinicalTrials. Gov identifier: NCT02221999 ); date of registration: Aug 20th, 2014.

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Hypermethylation of lncRNA MEG3 impairs chemosensitivity of breast cancer cells.

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Hypermethylation of lncRNA MEG3 impairs chemosensitivity of breast cancer cells.

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