Department of Thoracic and Cardiovascular Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, No. 114, Tianjin Street, Huangshi, 435000, Hubei, P.R. China.
BMC Cancer. 2022 Mar 22;22(1):308. doi: 10.1186/s12885-022-09404-8.
Several studies have documented the key role of microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). Although the expression of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene and miR-106b-5p are reportedly linked to cancer progression, their underlying mechanisms in ESCC remain unclear.
mRNA and miRNA expression in ESCC tissues and cells were analyzed using RT-qPCR. Luciferase and RNA pull-down assays were used to identify the interaction between miR-106b-5p and HPGD. Xenograft and pulmonary metastasis models were used to assess tumor growth and metastasis. CCK-8, BrdU, colony formation, adhesion, cell wound healing, Transwell, and caspase-3/7 activity assays, and flow cytometry and western blot analyses were used to examine the function of miR-106-5p and HPGD in ESCC cell lines.
The findings revealed that miR-106b-5p expression was upregulated in ESCC tissues and cell lines. miR-106b-5p augmented cellular proliferation, colony formation, adhesion, migration, invasion, and proportion of cells in the S-phase, but reduced apoptosis and the proportion of cells in G1-phase. Silencing of miR-106-5p inhibited tumor growth in vivo and pulmonary metastasis. Although HPGD overexpression suppressed proliferation, colony formation, adhesion, migration, and invasion of ESCC cells, it promoted apoptosis and caused cell cycle arrest of the ESCC cells. The results also indicated a direct interaction of HPGD with miR-106b-5p in ESCC cells. Furthermore, miR-106b-5p inhibited HPGD expression, thereby suppressing ESCC tumorigenesis.
Our data suggest that miR-106b-5p enhances proliferation, colony formation, adhesion, migration, and invasion, and induces the cycle progression, but represses apoptosis of ESCC cells by targeting HPGD. This suggests that the miR-106b-5p/HPGD axis may serve as a promising target for the diagnosis and treatment of ESCC.
多项研究表明，微小 RNA（miRNA）在食管鳞状细胞癌（ESCC）中发挥关键作用。尽管 15-羟基前列腺素脱氢酶（HPGD）基因和 miR-106b-5p 的表达与癌症进展有关，但它们在 ESCC 中的潜在机制尚不清楚。
使用 RT-qPCR 分析 ESCC 组织和细胞中的 mRNA 和 miRNA 表达。使用荧光素酶和 RNA 下拉测定来鉴定 miR-106b-5p 和 HPGD 之间的相互作用。使用异种移植和肺转移模型评估肿瘤生长和转移。CCK-8、BrdU、集落形成、黏附、细胞划痕愈合、Transwell 以及 caspase-3/7 活性测定和流式细胞术和 Western blot 分析用于检查 miR-106-5p 和 HPGD 在 ESCC 细胞系中的功能。
结果显示，miR-106b-5p 在 ESCC 组织和细胞系中表达上调。miR-106b-5p 增强了细胞增殖、集落形成、黏附、迁移、侵袭和 S 期细胞比例，但降低了细胞凋亡和 G1 期细胞比例。miR-106-5p 沉默抑制体内肿瘤生长和肺转移。虽然 HPGD 过表达抑制 ESCC 细胞的增殖、集落形成、黏附、迁移和侵袭，但它促进了细胞凋亡并导致 ESCC 细胞的细胞周期停滞。结果还表明 HPGD 在 ESCC 细胞中与 miR-106b-5p 直接相互作用。此外，miR-106b-5p 抑制 HPGD 表达，从而抑制 ESCC 肿瘤发生。
我们的数据表明，miR-106b-5p 通过靶向 HPGD 增强 ESCC 细胞的增殖、集落形成、黏附、迁移和侵袭，并诱导细胞周期进展，但抑制细胞凋亡。这表明 miR-106b-5p/HPGD 轴可能成为 ESCC 诊断和治疗的有希望的靶点。
