MicroRNA‑301a targets WNT1 to suppress cell proliferation and migration and enhance radiosensitivity in esophageal cancer cells

Abstract

Esophageal cancer (EC) is one of the leading causes of death among malignancies. Radiotherapy for esophageal squamous cell carcinoma (ESCC) patients is limited by resistance to ionizing radiation (IR). An increasing body of evidence has demonstrated that aberrant expression of microRNA-301a (miR-301a) contributes to cancer progression and sensitivity to radiation. The aim of the present study was to investigate the exact functions and potential mechanisms of miR-301a in ESCC radioresistance. Initially, the miR-301a-transfected radioresistant ESCC cells KYSE-150R exhibited a decreased proliferation rate, and enhanced radiosensitivity and migration, whereas downregulation of miR-301a in radiosensitive KYSE-150 cells produced the opposite results. miR-301a regulates WNT1 expression at both the mRNA and protein levels. Furthermore, dual-luciferase reporter assays revealed that WNT1 was a target gene of miR-301a. In addition, the expression of miR-301a markedly affected the expression of Wnt/β-catenin-related proteins such as β-catenin and cyclin D1. Finally, overexpression of miR-301a inhibited epithelial-mesenchymal transition (EMT) conversion by directly targeting Snail and vimentin in radioresistant-ESCC cell lines; however, no inhibitory effects were exerted on Twist. Collectively, these results indicated that miR-301a increased the radiosensitivity and inhibited the migration of radioresistant-ESCC cells by targeting WNT1, thereby inactivating the Wnt/β-catenin signaling pathway and EMT reversal. Thus, miR-301a may be a potential therapeutic target for the treatment of EC radioresistance.

MicroRNA‐1275 induces radiosensitization in oesophageal cancer by regulating epithelial‐to‐mesenchymal transition via Wnt/β‐catenin pathway

“…Fortunately, WNT1, a key molecule involved in Wnt/β‐catenin pathway, was predicted and verified as the direct target of miR‐1275 for the first time in this study, so that miR‐1275 negatively regulated Wnt/β‐catenin signalling in EC cells by targeting WNT1. Collectively, we proved that miR‐1275 affected EC radiosensitivity by targeting WNT1‐activated Wnt/β‐catenin pathway, and similar mechanism was previously unearthed in the influence of miR‐301a on the migration and radiosensitivity of EC cells . More importantly, the rescue of WNT1 on miR‐1275‐regulated EC radiosensitivity was mediated by the enhancement of WNT1‐regulated Wnt/β‐catenin signalling per se on EMT, thus indicating the strong association among miR‐1275, EMT and WNT1 in regulating the radiosensitization of EC cells.…”

“…Collectively, we proved that miR-1275 affected EC radiosensitivity by targeting WNT1-activated Wnt/β-catenin pathway, and similar mechanism was previously unearthed in the influence of miR-301a on the migration and radiosensitivity of EC cells. 43 More importantly, the rescue of WNT1 on miR-1275-regulated EC radiosensitivity was mediated by the enhancement of WNT1-regulated Wnt/β-catenin signalling per se on EMT, 44,45 thus indicating the strong association among miR-1275, EMT and WNT1 in regulating the radiosensitization of EC cells.…”

EphA5 knockdown enhances the invasion and migration ability of esophageal squamous cell carcinoma via epithelial-mesenchymal transition through activating Wnt/β-catenin pathway

“…It has been shown that Epithelial-mesenchymal transition (EMT) is associated with various tumor functions including tumor cell migration, invasion, and metastasis [18][19][20]. Several researchers have shown that EMT plays an important role in ESCC [21][22][23][24][25] and is associated with the prognosis of patients [25]. Thus, the expression of E-cadherin, N-cadherin, and Snail was measured in ESCC cells following EphA5 knocked down.…”

Role of non-coding RNAs and RNA modifiers in cancer therapy resistance

“…In contrast, some miRNAs are correlated to radiosensitivity. MiR301a enhances radiosensitivity and suppresses tumor cell migration via targeting WNT1 in EC, thus counteracting the Wnt//β-catenin signaling pathway and reversing EMT [154]. Similarly, miR-338-5p can improve radiosensitivity in vitro and in vivo through survivin [155].…”