Abstract
Drug resistance, whether intrinsic or acquired, often leads to treatment failure in esophageal squamous cell carcinoma (ESCC). Clarifying the mechanism of drug resistance in ESCC has great significance for reversing drug resistance, as well as improving the prognosis of patients. Previously, we demonstrated that etoposide-induced 2.4-kb mRNA (EI24) is the target of miR-483-3p, which promoted the growth, migration, and drug resistance in ESCC, suggesting that EI24 participates in repressing the tumorigenesis and progression of ESCC. Here, we observed that EI24 was remarkably decreased in ESCC tissues. Moreover, its expression was directly linked to the prognosis of patients. We then confirmed that the forced overexpression of EI24 repressed cell growth and sensitized ESCC cells to chemotherapeutic agents, whereas EI24 silencing had the opposite effect. Furthermore, gene microarray and ingenuity pathway analysis (IPA) were performed to establish the potential mechanisms and indicated that EI24 exerts a tumor-suppressive role via suppressing the acute phase response signaling pathway or IL-1 signaling pathway in ESCC. Collectively, our data reveal that EI24 overexpression attenuates malignant phenotypes of ESCC and that it is a novel possible ESCC therapeutic target.
Highlights
Esophageal cancer (EC) is the seventh most prevalent malignant cancer globally, ranking the sixth regarding causes of cancer-linked fatalities [1]
To establish if etoposideinduced 2.4-kb mRNA (EI24) was unusually expressed in esophageal squamous cell carcinoma (ESCC), estimation of the expression profile of EI24 in ESCC tissues was conducted by employing tissue microarray (TMA) involving 95 cases of human ESCC and 85 cases of corresponding paratumor tissues
The online Kaplan–Meier plotter tool confirmed that patients who had lower EI24 expression had a poor survival relative to the patients with elevated EI24 expression [hazard ratio (HR) = 0.37; 95% confidence interval (CI), 0.14–0.96, P = 0.034] (Figure 1D)
Summary
Esophageal cancer (EC) is the seventh most prevalent malignant cancer globally, ranking the sixth regarding causes of cancer-linked fatalities [1]. Over 572,034 new EC cases, as well as 508,585 fatalities that occurred in 2018, are responsible for approximately 4% of cancer cases and fatalities [2]. Esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) are the two subtypes of EC. ESCC accounts for approximately 88% of EC patients [3]. The initiation and development of ESCC present a gradual transformation process, from mild dysplasia to severe dysplasia, to carcinoma in situ, and to be an invasive cancer [4]. Several variables have been identified as predisposing risk factors for ESCC, including heavy smoking, low socioeconomic status, alcohol consumption, mycotoxin-contaminated or nitrosamine-rich foods, and nutritional deficiencies [2]
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