Department of Gastroenterology, Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028007, P.R. China.
Department of Endoscopy, Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028007, P.R. China.
Int J Mol Med. 2020 Dec;46(6):2007-2018. doi: 10.3892/ijmm.2020.4750. Epub 2020 Oct 9.
Long intergenic non‑coding RNA 01232 (LINC01232) was identified as a critical regulator of the development of pancreatic adenocarcinoma. The present study investigated the expression and regulatory roles of LINC01232 in esophageal squamous cell carcinoma (ESCC). The main aim of the present study was to elucidate the underlying mechanisms through which LINC01232 affects the malignancy of ESCC. Initially, LINC01232 expression in ESCC was analyzed using the TCGA and GTEx databases and was confirmed using reverse transcription‑quantitative polymerase chain reaction. ESCC cell proliferation, apoptosis and migration and invasion were assessed using the Cell Counting kit‑8 assay, flow cytometric analysis, and migration and invasion assays, respectively. ESCC tumor growth in vivo was examined using a xenograft mouse model. As shown by the results, a high LINC01232 expression was detected in ESCC tissues and cell lines. LINC01232 downregulation suppressed the proliferation, migration and invasion of ESCC cells, and promoted cell apoptosis in vitro. In addition, LINC01232 depletion restricted tumor growth in vivo. Mechanistically, LINC01232 was shown to function as an microRNA‑654‑3p (miR‑654‑3p) sponge in ESCC cells, and hepatoma‑derived growth factor (HDGF) was identified as a direct target of miR‑654‑3p. LINC01232 could bind competitively to miR‑654‑3p and decrease its expression in ESCC cells, thereby promoting HDGF expression. Rescue experiments reconfirmed that the effects of LINC01232 deficiency in ESCC cells were restored by increasing the output of the miR‑654‑3p/HDGF axis. On the whole, the present study demonstrates that LINC01232 plays a tumor‑promoting role during the progression of ESCC by regulating the miR‑654‑3p/HDGF axis. The LINC01232/miR‑654‑3p/HDGF pathway may thus provide a novel theoretical basis for the management of ESCC.
长链非编码 RNA 01232（LINC01232）被鉴定为胰腺腺癌发展的关键调节因子。本研究调查了 LINC01232 在食管鳞状细胞癌（ESCC）中的表达和调节作用。本研究的主要目的是阐明 LINC01232 影响 ESCC 恶性程度的潜在机制。本研究首先使用 TCGA 和 GTEx 数据库分析了 LINC01232 在 ESCC 中的表达，并通过逆转录-定量聚合酶链反应进行了验证。使用细胞计数试剂盒-8 测定法、流式细胞术分析和迁移和侵袭测定法分别评估 ESCC 细胞的增殖、凋亡以及迁移和侵袭。使用异种移植小鼠模型检测 ESCC 肿瘤的体内生长情况。结果表明，在 ESCC 组织和细胞系中检测到高表达的 LINC01232。LINC01232 下调抑制 ESCC 细胞的增殖、迁移和侵袭，并促进细胞凋亡。此外，LINC01232 耗竭限制了体内肿瘤的生长。机制上，LINC01232 被证明在 ESCC 细胞中作为 microRNA-654-3p（miR-654-3p）海绵起作用，并且肝癌衍生生长因子（HDGF）被鉴定为 miR-654-3p 的直接靶标。LINC01232 可以与 miR-654-3p 竞争结合，并降低 ESCC 细胞中的表达，从而促进 HDGF 的表达。挽救实验再次证实，通过增加 miR-654-3p/HDGF 轴的输出，可以恢复 ESCC 细胞中 LINC01232 缺失的作用。总的来说，本研究表明，LINC01232 通过调节 miR-654-3p/HDGF 轴在 ESCC 的进展中发挥促肿瘤作用。因此，LINC01232/miR-654-3p/HDGF 通路可能为 ESCC 的治疗提供新的理论依据。
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