Abstract
Esophageal squamous cell carcinoma (ESCC) ranks as one of the most deadly cancers worldwide due to its aggressive progression and poor treatment response. The long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) axis has been highlighted as a potency biomarker for enhancing the radiosensitivity of ESCC. Hence, we investigated the functional mechanism of the lncRNA DIO3OS/miR-130b/PAX9 axis in the radioresistance of ESCC cells. In cell experiments, we altered the miR-130b expression in ESCC cells using mimic or inhibitor to examine its effects on ESCC cell activities in response to 4 Gy irradiation, as well testing the involvement of lncRNA DIO3OS and the transcription factor gene PAX9. Tumor xenograft experiments were then conducted to observe the effect of miR-130b, lncRNA DIO3OS, and PAX9 on the radiosensitivity of ESCC cells in vivo. miR-130b was found to be highly expressed in ESCC. Downregulated miR-130b inhibited proliferation, invasion, and resistance to apoptosis in ESCC cells. LncRNA DIO3OS and PAX9 were downregulated in ESCC. The lncRNA DIO3OS could upregulate PAX9 by binding to miR-130b, which ultimately promoted the radiosensitivity of ESCC in vitro and in vivo. Taken together, lncRNA DIO3OS upregulates the expression of PAX9 by binding to miR-130b, ultimately promoting the radiosensitivity of ESCC.
Highlights
Esophageal squamous cell carcinoma (ESCC) ranks as one of the most fatal cancers worldwide for its aggression and unsatisfactory survival rate
The preliminary microarray analysis performed in the present study identified the binding of miR–130b to differentially expressed long noncoding RNA DIO3OS and paired box 9 (PAX9) gene, which led to a hypothesis of the involvement of the DIO3OS/miR–130b/PAX9 axis in the radiosensitivity of ESCC
reverse transcription quantitative polymerase chain reaction (RT-qPCR) was subsequently applied to detect the expression of miR–130b in ESCC cell lines (EC109, TE–1, KYSE70, KYSE270, and KYSE30) and human normal esophageal epithelial cells (HEEC) (Fig. 1C)
Summary
Esophageal squamous cell carcinoma (ESCC) ranks as one of the most fatal cancers worldwide for its aggression and unsatisfactory survival rate. Esophageal squamous cell carcinoma (ESCC) is a malignancy characterized by a high rate of morbidity and mortality largely due to the delayed diagnosis in high-grade stages, which has been reported to account for approximately 90% of all the EC cases on an annual basis globally [2]. In Chinese population, EC ranks as the fourth most prevalent malignancy and the fourth leading cause of cancer-related fatality, resulting in approximately 100 per 100,000 cases diagnosed annually [4]. The advancements in surgical methods and other treatment regimens improve prognosis of ESCC patients, ESCC still remains one of the most lethal cancers with a devastating 5-year survival rate in the advanced stage of less than 15% [8]. In order to increase overall survival and prevent radioresistance, novel therapies tailored with the aid of molecular biomarkers of ESCC are urgently required
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