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长链非编码 RNA ABHD11-AS1 通过竞争性结合 miR-330-5p 并上调 MARK2 促进宫颈癌的进展。

Long non-coding RNA ABHD11-AS1 facilitates the progression of cervical cancer by competitively binding to miR-330-5p and upregulating MARK2.

机构信息

Department of Gynecology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, 215001, Jiangsu, China.

Department of Gynecology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, 215001, Jiangsu, China.

出版信息

Exp Cell Res. 2022 Jan 1;410(1):112929. doi: 10.1016/j.yexcr.2021.112929. Epub 2021 Nov 16.

DOI:10.1016/j.yexcr.2021.112929
PMID:34793775
Abstract

Cervical cancer (CC) is among the most prevalent gynecological malignancies. Participation of long non-coding RNA (lncRNA) in modulating biological behaviors of CC cells has been confirmed. However, the function of lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) in CC is still unclear. RT-qPCR and Western blot were performed for measuring RNA and protein levels. Functional assays were done to evaluate ABHD11-AS1 influences on cell proliferation, apoptosis, invasion and migration. After the verification of ABHD11-AS1 distribution in CC cells, mechanism assays were conducted to study the interaction of relative RNAs. ABHD11-AS1 expression was abnormally high in CC cells. In vitro experiments showed ABHD11-AS1 downregulation restrained CC cell malignant phenotypes. In vivo experiments proved ABHD11-AS1 knockdown impeded tumor growth. Moreover, miR-330-5p was corroborated to bind with ABHD11-AS1 in CC cells and microtubule affinity regulating kinase 2 (MARK2) was confirmed to be targeted by miR-330-5p. MiR-330-5p inhibition or MARK2 overexpression could countervail the suppressive effect of ABHD11-AS1 knockdown on CC cell malignant behaviors. We found that ABHD11-AS1 facilitated CC tumorigenesis through competitively sequestering miR-330-5p to upregulate MARK2, indicating ABHD11-AS1 as a potential biomarker in CC.

摘要

宫颈癌(CC)是最常见的妇科恶性肿瘤之一。长链非编码 RNA(lncRNA)参与调节 CC 细胞的生物学行为已得到证实。然而,lncRNA ABHD11 反义 RNA 1(ABHD11-AS1)在 CC 中的功能尚不清楚。采用 RT-qPCR 和 Western blot 检测 RNA 和蛋白水平。通过功能测定评估 ABHD11-AS1 对细胞增殖、凋亡、侵袭和迁移的影响。验证 ABHD11-AS1 在 CC 细胞中的分布后,进行机制测定以研究相关 RNA 的相互作用。ABHD11-AS1 在 CC 细胞中表达异常升高。体外实验表明,ABHD11-AS1 下调抑制 CC 细胞恶性表型。体内实验证明 ABHD11-AS1 敲低抑制肿瘤生长。此外,在 CC 细胞中证实 miR-330-5p 与 ABHD11-AS1 结合,并且微管亲和调节激酶 2(MARK2)被证实是 miR-330-5p 的靶标。抑制 miR-330-5p 或过表达 MARK2 可以抵消 ABHD11-AS1 敲低对 CC 细胞恶性行为的抑制作用。我们发现 ABHD11-AS1 通过竞争性结合 miR-330-5p 促进 CC 肿瘤发生,从而上调 MARK2,表明 ABHD11-AS1 是 CC 中的潜在生物标志物。

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