MiR-106b-5p regulates esophageal squamous cell carcinoma progression by binding to HPGD

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

MicroRNA‐196a‐5p facilitates the onset and progression via targeting ITM2B in esophageal squamous cell carcinoma

“…23 Moreover, these heightened miR-106b-5p levels suppressed HPGD expression, which constituted crucial factors that impact the progression and prognosis of patients with ESCC. 24 Similar to numerous miRNAs, miR-196a-5p significantly contributed as a tumor-associated regulatory factor in various cancers. 25,26 Previous studies have confirmed that miR-196a-5p functioned as an oncogene in ESCC, displaying specific biological behaviors.…”

“…MiR‐601 could negatively regulating HDAC6, thereby inhibiting ESCC progression 23 . Moreover, these heightened miR‐106b‐5p levels suppressed HPGD expression, which constituted crucial factors that impact the progression and prognosis of patients with ESCC 24 . Similar to numerous miRNAs, miR‐196a‐5p significantly contributed as a tumor‐associated regulatory factor in various cancers 25,26 .…”

MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma

“…The increased expressions of miR-10b-3p, miR-106b-5p, miR-25, miR-320b, miR-602, miR-9, and miR-99b/Let-7e/miR-125a not only show significant correlations with metastasis in ESCC patients, but these miRNAs are also known to increase the invasion, migration, and/or EMT of ESCC cells. Additionally, these miRNAs can promote the metastasis of transplanted tumors, primarily to the lungs[ 52 - 58 ]. Other miRNAs, including miR-1269, miR-17-5p, miR-18a-5p, miR-25-3p, miR-301, miR-373, miR-483-5p, miR-766-3p, and others, display oncogenic roles in metastasis, affecting both ESCC tissues and cells[ 59 - 67 ].…”

Enhancing the therapeutic potential of curcumin: a novel nanoformulation for targeted anticancer therapy to colorectal cancer with reduced miR20a and miR21 expression

“…CRC and other malignancies have been linked to abnormal miRNA expression (Jiang et al 2015). Two miRNAs, miR-20 and miR-21, have been linked to the development and spread of CRC and be dysregulated in this disease (Yang et al 2022, Probst et al 2018.…”