The miR-199a-3p regulates the radioresistance of esophageal cancer cells via targeting the AK4 gene

Abstract

BackgroundMiRNAs was recognized as vital regulators involved in cancer development. Radioresistance remains a major obstacle for effective treatment of cancers. The mechanisms on the miRNA-mediated radioresistance of cancers are still poorly understood. The main subject of this study is to find new miRNA biomarker that regulates the radioresistance of esophageal cancer (EC).MethodsThe cumulative dose of radiation assays were used to screen the EC radioresistant cell lines. Wound-healing and invasion assays were used to characterize the properties of these cell lines. The following survival fraction experiments were performed to test the effects of miR-199a-3p and AK4 in the radioresistance of EC. In addition, we used the luciferase reporter assays to identify the putative underlying mechanism that relates to the miR-199a-3p regulated radio-resistance.ResultsWe found that the AK4 gene is one of the targets of miR-199a-3p, which promotes the radioresistance of EC cells. The following experiments by force reversal of the miR-199a-3p or AK4 levels confirmed the relationship of miR-199a-3p and AK4 with the radioresistance of EC cells. In addition, the activities of several signaling pathway were drastically altered by the forced changes of the miR-199a-3p level in EC cells.ConclusionTaken together, we found that miR-199a-3p can be potentially used as a biomarker for the EC radioresistance. Moreover, these results provides new insights into the mechanism on the radioresistance of EC cells, and also might guide the clinical therapy of EC.

Identification of AK4 as a novel therapeutic target for serous ovarian cancer

“…AK4 could modulate anticancer drug sensitivity in lung cancer via the regulation of mitochondrial activity ( 28 ). AK4 could also affect multi-chemoresistance and radioresistance in osteosarcoma and esophageal cancer, and AK4 expression was regulated by miR-199a-3p ( 21 , 29 ). Another study indicated that AK4 also affected the proliferation and invasion of bladder cancer cells in vitro ( 20 ).…”

“…The involvement of AK4 in the progression of multiple types of cancer has been investigated ( 17 – 21 ). AK4 has been associated with the clinical features of patients with lung cancer and promoted the metastasis of lung cancer by downregulating ATF3 ( 17 , 18 ).…”

“…Similarly, AK4 contributed to bladder cancer cell proliferation and invasion in vitro and in vivo ( 20 ). In esophageal cancer, microRNA (miR)-199a-3p, regulated the radioresistance of cancer cells by targeting AK4 ( 21 ). However, the possible role of AK4 in the progression and metastasis of SOC remains unclear.…”

miR‐16‐5p modulates the radiosensitivity of cervical cancer cells via regulating coactivator‐associated arginine methyltransferase 1

“…MiR‐153‐3p enhances the radiosensitivity of human glioma cells by targeting B cell lymphoma‐2 . MiR‐199a‐3p promotes radioresistance in esophageal cancer by targeting adenylate kinase 4 . In addition, miR‐16‐5p enhances the radiosensitivity of prostate cancer cells by modulating the Cyclin D1/E1‐pRb‐E2F1 signaling pathway .…”

Potential role of exosomes in cancer therapy

“…60 Radioresistance in cancer cells causes recurrence of diseases and treatment failure, which is a major clinical obstacle for the treatment by radiotherapy. 61,62 Exosomes modulate the radioresistance of head and neck cancer cells, as indicated by higher overall survival and accelerated DNA repair in cells treated with exosomes isolated from irradiated cells. 63 Exosomes derived from irradiated squamous head and neck carcinoma cells conferred a migratory phenotype to recipient cancer cells.…”