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Erb-B2 受体酪氨酸激酶 2 可被宫颈癌细胞中 p53 反应性 microRNA-3184-5p 负向调控。

Erb‑B2 Receptor Tyrosine Kinase 2 is negatively regulated by the p53‑responsive microRNA‑3184‑5p in cervical cancer cells.

机构信息

Department of Gynecological Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.

Department of Respiration and Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.

出版信息

Oncol Rep. 2021 Jan;45(1):95-106. doi: 10.3892/or.2020.7862. Epub 2020 Nov 19.

Abstract

The oncogenic role of Erb‑B2 Receptor Tyrosine Kinase 2 (ERBB2) has been identified in several types of cancer, but less is known on its function and mechanism of action in cervical cancer cells. The present study employed a multipronged approach to investigate the role of ERBB2 in cervical cancer. ERBB2 and microRNA (miR)‑3184‑5p expression was assessed in patient‑derived cervical cancer biopsy tissues, revealing that higher levels of ERBB2 and lower levels of miR‑3184‑5p were associated with clinicopathological indicators of cervical cancer progression. Furthermore, ERBB2 stimulated proliferation, migration and sphere‑formation of cervical cancer cells in vitro. This effect was mediated by enhanced phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit α activity. Additionally, it was revealed that miR‑3184‑5p directly suppressed ERBB2 in cervical cancer cells. The p53 activator Mithramycin A stimulated p53 and miR‑3184‑5p expression, thereby lowering the levels of ERBB2 and attenuating proliferation, migration and sphere‑formation of cervical cancer cells. In conclusion, the findings of the present study suggested ERBB2 as an oncogenic protein that may promote invasiveness in cervical cancer cells. Treatment of cervical cancer cells with the p53 activator Mithramycin A restored the levels of the endogenous ERBB2 inhibitor miR‑3184‑5p and may represent a novel treatment strategy for cervical cancer.

摘要

erb-B2 受体酪氨酸激酶 2(ERBB2)的致癌作用已在多种类型的癌症中得到鉴定,但在宫颈癌细胞中,其功能和作用机制知之甚少。本研究采用多管齐下的方法来研究 ERBB2 在宫颈癌中的作用。评估了患者来源的宫颈癌活检组织中 ERBB2 和 microRNA(miR)-3184-5p 的表达,结果表明 ERBB2 水平较高和 miR-3184-5p 水平较低与宫颈癌进展的临床病理指标相关。此外,ERBB2 刺激宫颈癌细胞在体外的增殖、迁移和球体形成。这种作用是通过增强磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚单位 α 的活性来介导的。此外,研究还表明 miR-3184-5p 可直接抑制宫颈癌细胞中的 ERBB2。p53 激活剂米托蒽醌 A 可刺激 p53 和 miR-3184-5p 的表达,从而降低 ERBB2 水平并减弱宫颈癌细胞的增殖、迁移和球体形成。总之,本研究的结果表明 ERBB2 是一种致癌蛋白,可能促进宫颈癌细胞的侵袭性。用 p53 激活剂米托蒽醌 A 处理宫颈癌细胞可恢复内源性 ERBB2 抑制剂 miR-3184-5p 的水平,这可能代表宫颈癌的一种新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29c9/7709819/ac64f653c21a/OR-45-01-0095-g00.jpg

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