miR-873 acts as a novel sensitizer of glioma cells to cisplatin by targeting Bcl-2

Abstract

Treatment with cisplatin, a chemotherapeutic agent commonly used in glioma patients, often results in chemoresistance. Increasing evidence has shown that microRNAs (miRNAs) are implicated in the drug resistance of gliomas. However, the function of miR‑873 in cisplatin resistance of gliomas remains unknown. In this study, we found that many miRNAs, including miR‑873, are differentially expressed in cisplatin-resistant glioma cells compared to wild-type glioma cells. Moreover, cisplatin reduced the expression of miR‑873 in a time-dependent manner. Overexpression of miR‑873 decreased the cell proliferation, migration and invasion while increased apoptosis of cisplatin-resistant glioma cells and sensitized the cells to cisplatin-induced cell growth arrest and apoptosis. Furthermore, miR‑873 was downregulated while Bcl-2 was upregulated in the tissues of twelve high-grade glioma patients compared to seven normal brain tissues, and the miR‑873 level was negatively correlated with the Bcl-2 protein level. A luciferase reporter assay further confirmed that Bcl-2 was a direct target of miR‑873, and miR‑873 decreased the level of the Bcl-2 protein in cisplatin-resistant glioma cells. Notably, re-expression of Bcl-2 attenuated the function of miR‑873 in cisplatin-resistant glioma cells and the sensitivity of the cells to cisplatin. Taken together, these data suggest that miR‑873 might be a potential marker for cisplatin resistance and a promising sensitizer in cisplatin treatment.

MiR‐873 inhibition enhances gefitinib resistance in non‐small cell lung cancer cells by targeting glioma‐associated oncogene homolog 1

“…Recent studies have found that miRNAs regulate drug resistance by mediating their targeting genes in various cancers . In recent years, abnormal expression of miR‐873 has been found in many kinds of tumors, such as breast and ovarian cancers, and glioma . MiR‐873 plays a role in promoting cancer or anticancer by regulating tumor cell invasion, migration, proliferation, apoptosis, and sensitivity to chemotherapeutic drugs .…”

“…[20][21][22][23][24] In recent years, abnormal expression of miR-873 has been found in many kinds of tumors, such as breast and ovarian cancers, and glioma. [25][26][27] MiR-873 plays a role in promoting cancer or anticancer by regulating tumor cell invasion, migration, proliferation, apoptosis, and sensitivity to chemotherapeutic drugs. [28][29][30][31] Nevertheless, the role of miR-873 in drug resistance in NSCLC is still unknown.…”

Up‐regulation of miR‐497 confers resistance to temozolomide in human glioma cells by targeting mTOR/Bcl‐2

“…Recent evidence has shown that miRNAs also plays a vital role in chemotherapeutic resistance. For instance, miR‐873 was found to improve the chemosensitivity of glioblastoma cells to cisplatin by targeting Bcl‐2 . MiR‐16 was reported to mediate TMZ resistance in glioma cells by modulation of apoptosis , highlighting miRNAs as potent chemo‐resistant modulators in the treatment of glioma.…”

MicroRNA‑873 serves a critical role in human cervical cancer proliferation and metastasis via regulating glioma‑associated oncogene homolog 1

“…Li et al (10) further demonstrated that miR-873 reverses the EMT in colon cancer by negatively regulating the expression of ZEB1. This miRNA has also been reported to be downregulated in glioma tissues and to enhance chemoresistance to cisplatin by targeting Bcl-2 (19). However, another study revealed that miR-873 expression is upregulated in lung adenocarcinoma, and that this miRNA increases the proliferation and metastasis of these cells by regulating the tumor suppressor gene SRCIN1 (15).…”

“…Previous studies have also revealed that abnormal expression of miR-873 occurs in various types of cancer, such as breast, lung, colorectal and ovarian cancer, and glioma (9)(10)(11)(12)(13)(14)(15)(16)(17). Notably, miR-873 is crucial for paclitaxel and cisplatin sensitivity in ovarian cancer and cisplatin sensitivity in glioma (18,19). However, the expression and function of miR-873 in cervical cancer are not fully understood.…”