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.
Keywords: endometrial carcinoma Kca3.1, lncRNA-14327.1, metastasis, EMT