Overexpression of miR-26b decreases the cisplatin-resistance in laryngeal cancer by targeting ATF2

Abstract

Cisplatin is a common used chemotherapeutic drug for the treatment of laryngeal cancer. However, drug-resistance is a major obstacle in platinum-based chemotherapy for laryngeal cancer. Recent studies have demonstrated that dysregulation of microRNAs (miRNAs) is responsible for chemoresistance in multiple cancers including laryngeal cancer, but the potential mechanisms are required to be explored. In the present study, we constantly exposed the laryngeal cancer cell line Hep-2 with cisplatin to establish a cisplatin-resistant laryngeal cancer cell model (Hep-2/R). We found that Hep-2/R cells exhibited obvious resistance to cisplatin compared to the Hep-2 cells. However, overexpression of miR-26b significantly decreased the half maximal inhibitory concentration (IC50) of cisplatin to Hep-2/R. Mechanically, miR-26b in Hep-2/R decreased the expression of ATF2, and thus inhibiting the phosphorylation of ATF2 and formation of cellular ATF2-c-Jun complex induced by cisplatin. As the results, Hep-2/R cells failed to overexpress the Bcl-xl which is a key anti-apoptotic protein under the cisplatin treatment. Therefore, overexpression of miR-26b was found to be able to promote mitochondrial apoptosis induced by cisplatin.

The activating transcription factor 2: an influencer of cancer progression

“…In comparison to therapy-sensitive cells, osteosarcoma, laryngeal and renal treatment-resistant cancer cells displayed reduced levels of miR-34a, miR-26b and miR-451, respectively. miR-26b and miR-451 were shown to directly regulate ATF2 through binding to its 3´UTR (87,88). On the other hand, miR-34a modulation of ATF2 was shown indirectly as overexpression of this miRNA resulted in increased ATF2 expression (89).…”

<p>Long Non-Coding RNA KCNQ1OT1 Promotes Multidrug Resistance in Chordoma by Functioning as a Molecular Sponge of miR-27b-3p and Subsequently Increasing ATF2 Expression</p>

“… 22 Notably, research indicated suppressing ATF2 expression decreases the cisplatin-resistance in tumor. 23 In this study, we found upregulation of miR-27b-3p weakens MDR in chordoma and ATF2 is a direct target of miR-27b-3p.…”

MiR‐26b suppresses hepatocellular carcinoma development by negatively regulating ZNRD1 and Wnt/β‐catenin signaling

“…Emerging studies have revealed that dysregulation of miRNAs are involved in different kinds of malignancies developmental processes. Among them, MiR‐26b has been documented to be frequently downregulated in multiple cancers, such as gastric cancer, breast cancer, esophageal squamous cancer, prostate cancer, lung cancer, laryngeal cancer, and HCC . On the contrary, the expression of miR‐26b is elevated in colorectal cancer, and miR‐26b overexpression could promote metastasis .…”

“…Among them, MiR-26b has been documented to be frequently downregulated in multiple cancers, such as gastric cancer, breast cancer, esophageal squamous cancer, prostate cancer, lung cancer, laryngeal cancer, and HCC. [10][11][12][13][14][15][16][17] On the contrary, the expression of miR-26b is elevated in colorectal cancer, and miR-26b overexpression could promote metastasis. 18,19 Therefore, the functional roles of miR-26b in human tumors varied between different cancer types.…”