MiR‐200c inhibits autophagy and enhances radiosensitivity in breast cancer cells by targeting UBQLN1

Abstract

Radioresistance is a major challenge during the treatment of breast cancer. A further understanding of the mechanisms of radioresistance could provide strategies to address this challenge. In our study, we compared the expression of miR- Breast cancer is the most common cancer in women worldwide. 1 Radiotherapy is an important part of the treatment in most patients receiving breast-conserving surgery and displays significant clinical benefits, such as decreasing the risk of local recurrence and reducing the risk of mortality due to breast cancer. 2 However, for certain subtypes of breast cancer (e.g., basal-like), the local and regional control remains unsatisfactory. A major reason for this failure in treatment may be due to its radioresistance. 3-5 Therefore, understanding the molecular mechanisms involved in the radioresistance of breast tumors may lead to improved clinical outcomes.Autophagy is a cellular process that involves selfdegradation and recycling of macromolecules and cellular organelles. 6,7 It is, in most circumstances, a prosurvival mechanism under stressful conditions. Autophagy has been implicated in a variety of human diseases. [7][8][9] Similar to the situation in normal cells, autophagy is also critical for tumor cells to survive stressful conditions, and thus has been implicated in tumor resistance to chemotherapy and radiotherapy. [10][11][12][13] MicroRNAs (miRNAs) regulate a variety of biological processes, including cell proliferation, differentiation and invasion. 14 Dysregulation of miRNAs has been reported to contribute to cancer, 15,16 and implicated in chemoresistance and radioresistance via modulation of autophagy. 10,13 Such findings are not surprising considering the fact that miRNAs are key regulators of autophagy. 17 The miR-200 family is involved in the self-renewal of cancer stem cells, 18 epithelial-to-mesenchymal transition (EMT) 19,20 and chemosensitivity. 21 Recent studies indicated that miR-200c, the prevailing member of the miR-200 family, 19,20,22,23 could sensitize cancer cells to radiation by targeting TBK1 and VEGF-VEGFR2, despite the unspecified relationship between miR-200c and autophagy. 24,25 The results from our study showed that miR-200c could sensitize breast cancer cells to radiation via a mechanism associated with inhibition of irradiation-induced autophagy.

miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance

“…Recently, another target of miR-200c, ubiquilin 1, has been shown to positively regulate radio-resistance by enhancing IR-induced autophagy in MDA-MB-231 breast cancer cells. Ectopic expression of miR-200c reversed the phenotype and sensitized the cells to radiation [71]. Furthermore, nanoparticle-assisted delivery of miR-200c has been shown to inhibit CSC-like properties and to augment radiosensitivity in three different gastric cancer cell lines [72].…”

Crosstalk between autophagy and intracellular radiation response (Review)

“…A large amount of recent studies have shown that tumor resistance to radiation therapy is often associated with the upregulation of autophagy in many kinds of tumor cell lines, such as colon cancer cells, prostate cancer cells, malignant glioma cells, nasopharyngeal carcinoma cells, and breast cancer cells (17,18). The putative cytoprotective function of autophagy induced by radiation is generally considered to reflect the capacity of the cell to eliminate toxic species such as free radicals and damaged and unwanted proteins or organelles to generate energy and metabolic precursors (19).…”

MicroRNA-129 in Human Cancers: from Tumorigenesis to Clinical Treatment

“…Recently, autophagy has been publicized to play a critical role in tumorigenesis. MiRNAs were identified to modulate cancer chemo-and radio-sensitivity via autophagy [81,82]. It was reported that norcantharidin (NCTD) could suppress miR-129-5p to provoke autophagic cell death and cell proliferation arrest in prostate cancer cells, which may increase cell autophagy via Beclin-1 as an initial cellular response to the toxicity of NCTD [83].…”