Department of Gastroenterology, Linyi Traditional Chinese Medical Hospital, Linyi, Shandong, China.
Department of Urology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.
Bioengineered. 2021 Dec;12(1):6687-6702. doi: 10.1080/21655979.2021.1973775.
Esophageal cancer (ESCA), as a common cancer worldwide, is a main cause of cancer-related mortality. Comprehensive studies on molecular mechanism of ESCA have been carried out. Though numerous long noncoding RNAs (lncRNAs) was reported to participate in the occurrence and development of ESCA, the potential role of lncRNA potassium calcium-activated channel subfamily M regulatory beta subunit 2 (KCNMB2) antisense RNA 1 (KCNMB2-AS1) in ESCA remains to be discovered. This study intends to investigate the detailed function and molecular mechanism of KCNMB2-AS1 in ESCA. Gene expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was examined by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell invasion and migration were measured by wound healing assay and Transwell assay. Luciferase reporter assay was adopted to validate the interaction between KCNMB2-AS1 and miR-3194-3p. Western blotting was performed to assess protein levels. We discovered that KCNMB2-AS1 was significantly upregulated in ESCA. KCNMB2-AS1 downregulation suppressed the growth, invasion, migration and stemness of ESCA cells. KCNMB2-AS1 bound with miR-3194-3p, and glycogen phosphorylase L (PYGL) was a direct target of miR-3194-3p. KCNMB2-AS1 upregulated PYGL expression by directly binding with miR-3194-3p. Additionally, PYGL overexpression abolished the inhibitory influence of KCNMB2-AS1 depletion on ESCA cell behaviors. Collectively, lncRNA KCNMB2-AS1 promotes ESCA development through targeting the miR-3194-3p/ PYGL axis, which might provide theoretical basis to explore novel biomarkers for ESCA treatment.
食管癌（ESCA）作为一种全球常见的癌症，是癌症相关死亡率的主要原因。已经对 ESCA 的分子机制进行了综合研究。尽管已经报道了许多长非编码 RNA（lncRNA）参与 ESCA 的发生和发展，但 lncRNA 钾钙激活通道亚家族 M 调节β亚基 2（KCNMB2）反义 RNA 1（KCNMB2-AS1）在 ESCA 中的潜在作用仍有待发现。本研究旨在探讨 KCNMB2-AS1 在 ESCA 中的详细功能和分子机制。通过逆转录定量聚合酶链反应（RT-qPCR）评估基因表达。通过细胞计数试剂盒-8（CCK-8）测定和集落形成测定来检测细胞增殖。通过划痕愈合测定和 Transwell 测定来测量细胞侵袭和迁移。采用荧光素酶报告基因测定验证 KCNMB2-AS1 和 miR-3194-3p 之间的相互作用。通过 Western blot 测定评估蛋白质水平。我们发现 KCNMB2-AS1 在 ESCA 中显著上调。KCNMB2-AS1 的下调抑制 ESCA 细胞的生长、侵袭、迁移和干性。KCNMB2-AS1 与 miR-3194-3p 结合，糖原磷酸化酶 L（PYGL）是 miR-3194-3p 的直接靶标。KCNMB2-AS1 通过直接与 miR-3194-3p 结合上调 PYGL 表达。此外，PYGL 过表达消除了 KCNMB2-AS1 耗竭对 ESCA 细胞行为的抑制影响。总之，lncRNA KCNMB2-AS1 通过靶向 miR-3194-3p/PYGL 轴促进 ESCA 的发展，这可能为探索 ESCA 治疗的新生物标志物提供理论依据。
