Esophageal squamous cell carcinoma (ESCC) is the most prevalent type in esophageal cancers. Despite accumulating achievements in treatments of ESCC, patients still suffer from recurrence because of the treatment failures, one of the reasons for which is radioresistance. Therefore, it is a necessity to explore the molecular mechanism underlying ESCC radioresistance. Long intergenic noncoding RNA 473 (LINC00473) has been reported to be aberrantly expressed in several human malignancies. However, its biological function in radiosensitivity of ESCC remains to be fully understood. This study explored the role of LINC00473 in radiosensitivity of ESCC cells and whether LINC00473 acted as a competing endogenous RNA to realize its modulation on radioresistance. We found that LINC00473 was markedly upregulated in ESCC tissues and cell lines, and its expression was remarkably related to cellular response to irradiation. In addition, knockdown of LINC00473 could sensitize ESCC cells to radiation in vitro. As for the underlying mechanism, we uncovered that there was a mutual inhibition between LINC00473 and miR‐374a‐5p. Spindlin1 (SPIN1) was verified as a downstream target of miR‐374a‐5p, and LINC00473 upregulated SPIN1 expression through negatively modulating miR‐374a‐5p expression. Furthermore, we revealed that SPIN1 could aggravate the radioresistance of ESCC cells. Finally, overexpression of SPIN1 reversed the LINC00473 silencing‐enhanced radiosensitivity in ESCC cells. To sum up, we demonstrated that LINC00473 facilitated radioresistance by regulating the miR‐374a‐5p/SPIN1 axis in ESCC.

The radioresistance of esophageal squamous cell carcinoma is a great obstacle to treatment. Although it has been demonstrated that microRNA-21 (miR-21) can act as an 'oncogene' in esophageal squamous cell carcinoma, its role in radioresistance remains unexplored. The aims of this study were to investigate the role of miR-21 in esophageal squamous carcinoma cells' radioresistance and to identify the possible mechanism. The relatively radioresistant esophageal squamous cancer TE-1 cells (TE-R60) was established by fractionated irradiation. By lentiviral transduction with miRZip-21, the miR-21 expression in TE-1 cells was stably downregulated, which was renamed as 'anti-miR-21 TE-1 cells.' The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was knocked down in anti-miR-21 TE-1 cells through short interfering RNA. The expression level of miR-21 and PTEN messenger RNA were measured by quantitative real-time reverse transcription polymerase chain reaction or reverse transcription polymerase chain reaction. The expression level of PTEN, phospho-Akt, and Akt protein were detected by Western blot. Clongenic assay was used to analyze the cells' radiosensitivity. miR-21 was overexpressed, and PTEN was suppressed in established radioresistant TE-R60 cells compared with the parent cells (1.3-fold and 70.83%). The inhibition of miR-21 significantly increased the cells' radiosensitivity (P < 0.05) and the PTEN protein expression (2.3-fold) in TE-1 cells. In addition, phospho-Akt protein, downstream target of PTEN, reduced significantly in anti-miR-21 TE-1 cells. Knockdown of PTEN in anti-miR-21 TE-1 cells could abrogate the miR-21 inhibition-induced radiosensitization (P < 0.05). Inhibition of miR-21 increased radiosensitivity of esophageal cancer TE-1 cells, and this effect was possibly through the activation of PTEN. Inhibition of miR-21 may form a novel therapeutic strategy to increase the radiosensitivity of esophageal cancer.