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Hsa_circ_0039569 通过靶向 miR-197/高迁移率族蛋白 A1 轴促进子宫内膜癌的进展。

Hsa_circ_0039569 facilitates the progression of endometrial carcinoma by targeting the miR-197/high mobility group protein A1 axis.

机构信息

Third Department of Gynecology and Oncology, Hunan Cancer Hospital, Changsha, Hunan Province, China.

Department of General Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

出版信息

Bioengineered. 2022 Feb;13(2):4212-4225. doi: 10.1080/21655979.2022.2027060.

DOI:10.1080/21655979.2022.2027060
PMID:35130798
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8973714/
Abstract

Circular RNAs are novel regulators in endometrial carcinoma. Hsa_circ_0039569 was reportedly upregulated in endometrial carcinoma; however, the functional roles and mechanisms of hsa_circ_0039569 need further investigation. Therefore, we used quantitative real-time PCR (qRT-PCR) to determine the mRNA levels of hsa_circ_0039569, miR-197 and high mobility group protein A1 (HMGA1). The protein level of HMGA1 was determined by Western blot. Cell Counting Kit-8 and colony formation assays were used to assess cell proliferation. Cell migration was measured via wound healing and Transwell assays. Transwell assay was also performed to determine cell invasion ability. Direct binding of the indicated molecules were verified by RNA binding protein immunoprecipitation (RIP) assay and dual luciferase reporter assay. The results revealed that hsa_circ_0039569 and HMGA1 were elevated, while miR-197 was downregulated in endometrial carcinoma. Moreover, hsa_circ_0039569 was positively correlated with the expression of HMGA1 and was negatively correlated with the level of miR-197. In addition, hsa_circ_0039569 facilitated the proliferation, migration and invasion of endometrial carcinoma cells. The underlying mechanism is that hsa_circ_0039569 serves as a sponge of miR-197 to repress the inhibitory effect of miR-197 on HMGA1. Furthermore, the miR-197/HMGA1 axis was implicated in endometrial carcinoma progression accelerated by hsa_circ_0039569. Collectively, hsa_circ_0039569 may promote the development of endometrial carcinoma by serving as an endogenous sponge of miR-197, increasing HMGA1 expression and identifying a novel target for endometrial carcinoma treatment.

摘要

环状 RNA 是子宫内膜癌中的新型调控因子。据报道,hsa_circ_0039569 在子宫内膜癌中上调;然而,hsa_circ_0039569 的功能作用和机制仍需要进一步研究。因此,我们使用实时定量 PCR (qRT-PCR) 来确定 hsa_circ_0039569、miR-197 和高迁移率族蛋白 A1 (HMGA1) 的 mRNA 水平。通过 Western blot 测定 HMGA1 的蛋白水平。使用细胞计数试剂盒-8 和集落形成实验评估细胞增殖。通过划痕愈合和 Transwell 实验测定细胞迁移。Transwell 实验也用于测定细胞侵袭能力。通过 RNA 结合蛋白免疫沉淀 (RIP) assay 和双荧光素酶报告基因assay 验证指示分子的直接结合。结果表明,在子宫内膜癌中,hsa_circ_0039569 和 HMGA1 上调,而 miR-197 下调。此外,hsa_circ_0039569 与 HMGA1 的表达呈正相关,与 miR-197 的水平呈负相关。此外,hsa_circ_0039569 促进子宫内膜癌细胞的增殖、迁移和侵袭。其潜在机制是 hsa_circ_0039569 作为 miR-197 的海绵,抑制 miR-197 对 HMGA1 的抑制作用。此外,miR-197/HMGA1 轴参与了 hsa_circ_0039569 加速的子宫内膜癌进展。总之,hsa_circ_0039569 可能通过作为 miR-197 的内源性海绵,增加 HMGA1 的表达,为子宫内膜癌的治疗提供新的靶点,从而促进子宫内膜癌的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/d2ce97a13706/KBIE_A_2027060_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/87271867452e/KBIE_A_2027060_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/036ed0c470b6/KBIE_A_2027060_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/67f56a128a5c/KBIE_A_2027060_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/cee39edb322d/KBIE_A_2027060_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/ca7afc83604d/KBIE_A_2027060_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/6b30783ae587/KBIE_A_2027060_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/822d0a58e369/KBIE_A_2027060_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/d2ce97a13706/KBIE_A_2027060_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/87271867452e/KBIE_A_2027060_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/036ed0c470b6/KBIE_A_2027060_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/67f56a128a5c/KBIE_A_2027060_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/cee39edb322d/KBIE_A_2027060_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/ca7afc83604d/KBIE_A_2027060_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/6b30783ae587/KBIE_A_2027060_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/822d0a58e369/KBIE_A_2027060_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b022/8973714/d2ce97a13706/KBIE_A_2027060_F0008_OC.jpg

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