<p>MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin</p>

Abstract

Background: The presence of glioma stem cells (GSCs) is thought to be a key factor responsible for development of the incurable glioblastoma multiforme (GBM). GSCs are often displayed during chemotherapy resistance, except for demethoxycurcumin (DMC), a component of curcumin, which has been previously confirmed to inhibit GSCs proliferation and induce apoptosis. Purpose: The objective of this study was to identify the main mechanism underlying anti-GSCs resistance by DMC. Patients and methods: qRT-PCR was used to determine the expression of miR-145 in glioma patients and GSCs, and GSCs were transfected with miR-145 overexpressed vectors. Then, functional analyses (in vitro and in vivo) were performed to confirm the role of miR-145 and DMC in GSCs. Finally, related proteins were tested by immunohistochemistry and Western blot. Results: miR-145 was atypically low-expressed miRNA in GSCs, and could enhance GSC chemosensitivity to DMC both in vitro and in vivo. Upregulation of miR-145 in GSCs resulted in increased cell growth inhibition and apoptosis to DMC. Further research on the mechanism demonstrated that the combined effects of miR-145 and DMC were involved in the miR-145/SOX2-Wnt/β-catenin pathway. Overexpression of SOX2 reduced GSC resistance to growth inhibition by miR-145+ DMC treatment. Conclusion: Our data strongly support an important role for miR-145 in enhancing GSC chemosensitivity to DMC by targeting the SOX2-Wnt/β-catenin axis.

MiR‐145 in cancer therapy resistance and sensitivity: A comprehensive review

“…MiR‐145 enhanced chemosensitivity to demethoxycurcumin by targeting the SOX2‐Wnt/β‐catenin axis in glioma. SOX2, a pluripotent stem cell marker, plays a pivotal role in maintaining the undifferentiated situation and proliferation of stem cells 12 . CREB‐binding protein (CBP) is a Wnt signaling component, and is frequently activated in nasopharyngeal carcinoma.…”

“…Researchers are currently attempting to explore the target genes of miR‐145 and their signaling pathways involved in altering therapeutic response, which is significant for the development of miRNA‐related therapies. Strikingly, various research has disclosed that miR‐145 acts in reversion of therapeutic resistance in multiple tumors, including lung cancer, 3‐6 esophageal squamous cell carcinoma (ESCC), 7‐9 ovarian carcinoma, 10,11 glioma, 12,13 hepatocellular carcinoma (HCC), 14‐16 breast cancer, 17 colorectal cancer (CRC) 18‐21 prostate cancer, 22,23 bladder cancer, 24 gastric cancer (GC), 25,26 pancreatic adenocarcinoma 27 and cervical cancer 28,29 …”

Long noncoding RNA MACC1-AS1 promotes the stemness of hepatocellular carcinoma cells by antagonizing miR-145

“…The regulation of CSCs is a complex process, involving a variety of signaling pathways, such as the Wnt/b-catenin, Notch, transforming growth factor (TGF)b, and interleukin (IL)-6/STAT3 signaling pathways. Previous studies have shown that miR-145 can enhance the chemosensitivity of glioma stem cells to demethoxycurcumin 16 and regulate the epithelial-mesenchymal transition (EMT) process in osteosarcoma. 17 Additionally, lncRNA Linc-DYNC2H1-4 promotes CSC phenotypes by acting as a sponge of miR-145 in pancreatic cancer cells.…”

MicroRNAs at the Crossroad of the Dichotomic Pathway Cell Death vs. Stemness in Neural Somatic and Cancer Stem Cells: Implications and Therapeutic Strategies

“…miR-145 is expressed at very low levels in GSCs, which is associated with increased tumorigenesis. Though, when experimentally induced, it increases U87 GSC apoptosis by inhibiting BNIP3 and Notch signaling [ 125 , 126 ]. Moreover, targeting of SRY-box transcription factor 9 ( SOX9 ) and adducin 3 ( ADD3 ) by miR-145 has been reported, consistent with increased apoptosis [ 127 ].…”