The Long Non-Coding RNA-14327.1 Promotes Migration and Invasion Potential of Endometrial Carcinoma Cells by Stabilizing the Potassium Channel Kca3.1
The Long Non-Coding RNA-14327.1 Promotes Migration and Invasion Potential of Endometrial Carcinoma Cells by Stabilizing the Potassium Channel Kca3.1
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长非编码RNA-14327.1通过稳定钾通道Kca3.1促进子宫内膜癌细胞的迁移和侵袭潜力
DOI：
10.2147/ott.s226737
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发表时间：
2019-11
期刊：
影响因子：
--
通讯作者：
Tao Zhu
中科院分区：
文献类型：
--
作者：
Yingli Zhang;Ping Zhang;Lu Chen;Lingqin Zhao;Jianqing Zhu;Tao Zhu
背景：中电导Ca2+激活钾通道（Kca3.1）在维持细胞内Ca2+稳态中发挥关键作用，并参与包括子宫内膜癌在内的许多人类肿瘤的癌变。然而，其潜在机制仍有待进一步阐明。方法：利用UALCAN癌症数据库分析Kca3.1与子宫内膜癌临床病理特征的关系，并采用免疫组化法检测其表达情况。使用RNA免疫沉淀测序测定在子宫内膜癌细胞系中筛选Kca3.1结合候选lncRNA。 MTT法和Transwell法分别用于确认细胞增殖、迁移和侵袭。 FACS用于测定细胞周期分布。通过qRT-PCR检测lncRNA的过表达效率。采用Western blot法分析EMT相关蛋白的表达及Kca3.1的稳定性。结果：Kca3.1与子宫内膜癌的肿瘤分期等临床病理特征相关。通过 RNA 免疫沉淀测序测定获得了几种 Kca3.1 结合 lncRNA。候选lncRNA之一lncRNA-14327.1的稳定表达导致Kca3.1蛋白水平、细胞迁移和侵袭能力显着上调，但抑制细胞增殖并诱导细胞周期停滞。此外，我们的数据还表明，Lenti-lncRNA-14327.1 可以稳定 Kca3.1 蛋白，从而增加细胞内 Ca2+ 浓度。转染siRNA-Kca3.1显着抑制细胞迁移和侵袭，并减弱Lenti-lncRNA-14327.1稳定表达的子宫内膜癌细胞的EMT。结论：综上所述，我们的结果表明lncRNA-14327.1通过稳定Kca3.1蛋白促进子宫内膜癌细胞的细胞迁移和侵袭潜力，这意味着lncRNA-14327.1/Kca3.1可能是子宫内膜癌，特别是转移性子宫内膜癌的一个有前途的治疗靶点。
Background: The intermediate-conductance Ca2+-activated potassium channel (Kca3.1) plays a key role in maintaining intracellular Ca2+ homeostasis and is involved with the carcinogenesis of many human tumors including endometrial carcinoma. However, the underlying mechanism is still remained to be further elucidated. .Methods: The relationship between Kca3.1 and the clinicopathological characteristics of endometrial carcinoma was analyzed using UALCAN cancer database, and its expression was determined by immunohistochemistry. The Kca3.1 binding candidate lncRNAs were screened using RNA immunoprecipitation sequencing assay in the endometrial carcinoma cell line. MTT assay and transwell assay were used to confirm the cell proliferation migration and invasion, respectively. FACS was used to determine the cell cycle distribution. The overexpression efficiency of the lncRNAs was detected by qRT-PCR. The expression of EMT related proteins and the stability of Kca3.1 were analyzed by Western blot assay..Results: Kca3.1 is related to clinicopathological characteristics of endometrial carcinoma, such as tumor stages. Several Kca3.1 binding lncRNAs were obtained from RNA immunoprecipitation sequencing assay. Stable expression of lncRNA-14327.1, one of the candidate lncRNAs, led to significant upregulation of Kca3.1 protein level, cell migration and invasion abilities, but suppressed cell proliferation and induced cell cycle arrest. Additionally, our data also demonstrated that Lenti-lncRNA-14327.1 could stabilize the protein of Kca3.1 and subsequently.increase intracellular Ca2+ concentration. Transfection of siRNA-Kca3.1 significantly inhibited.cell migration and invasion, and attenuated the EMT in Lenti-lncRNA-14327.1 stably expressed.endometrial carcinoma cells..Conclusion: Taken together, our results demonstrated that the lncRNA-14327.1 promoted cell migration and invasion potential of endometrial carcinoma cells by stabilizing Kca3.1 protein, implying that the lncRNA-14327.1/Kca3.1 might be a promising therapeutic target in endometrial carcinoma, particularly the metastatic one.
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影响因子：
8.8
作者：
Pillozzi S;D'Amico M;Bartoli G;Gasparoli L;Petroni G;Crociani O;Marzo T;Guerriero A;Messori L;Severi M;Udisti R;Wulff H;Chandy KG;Becchetti A;Arcangeli A
通讯作者：
Arcangeli A
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
DOI：
10.26355/eurrev_201808_15617
发表时间：
2018-08
影响因子：
3.3
作者：
L. Zhang;D-L Wang;YU P.
通讯作者：
L. Zhang;D-L Wang;YU P.
影响因子：
4
作者：
De Marchi, Umberto;Sassi, Nicola;Zoratti, Mario
通讯作者：
Zoratti, Mario