Project description:Chemotherapy remains the primary treatment of advanced solid cancer, including lung cancer. As first line treatment, cisplatin-based therapy is restricted by frequent development of drug resistance. Increasing data showed that programmed cell death protein ligand 1 (PD-L1) plays a vital role in regulating cisplatin resistance. However, the mechanisms underlying are not fully understood. We found miR-526b-3p expression declined while PD-L1 elevated in cisplatin-resistant lung cancer compared to that in cisplatin-sensitive lung cancer by analyzing clinical samples. Importantly, miR-526b-3p was associated with response to cisplatin negatively. We further demonstrated that miR-526b-3p reversed cisplatin resistance, suppressed metastasis, and activated CD8+ T cells in a STAT3/PD-L1-dependent manner. Our findings extended the knowledge of PD-L1-mediated cisplatin resistance of lung cancer. In addition, the introduction of miR-526b-3p provided a new clue to improve the anti-tumor effects of the combination of immunotherapy and chemotherapy. miProfileTM Cancer miRNA qPCR Array
Project description:Platinum resistance is a major drawback in the treatment of ovarian cancer. Evidence suggests that microRNAs are key players in the initiation, progression, and drug resistance of cancer cells. However, the precise miRNAs dysregulated and contributing to platinum resistance in ovarian cancer cells have not been fully elucidated. Here, we conducted a miRNA expression profiling of cisplatin-sensitive (A2780) and cisplatin-resistant (CP20 and CIS) ovarian cancer cells to identify potential miRNAs involved in platinum resistance.
Project description:miRNA was extracted from a range of Oesophageal Adenocarcinoma cell lines using the miRNeasy Mini Kit (Qiagen, #217004, Chadstone, Australia) and RNase-free DNase Set (Qiagen, #79254, Chadstone, Australia). miRNA was reverse transcribed using a Custom OpenArray® miRNA RT pool (Life Technologies cat # A25630) and the TaqMan® microRNA Reverse Transcription Kit (Life Technologies cat # 4366596). cDNA Pre-amplifications were carried out with a Custom OpenArray® PreAmp pool (Life Technologies cat # 4485255) and TaqMan PreAmp Master Mix (Life Technologies cat # 4488593). PCR runs were performed using a QuantStudio™ 12K Flex Real-Time PCR System. Baseline qPCR expression profiling of miRNAs from 8 oesophageal Adenocarcinoma cell lines, prior to treating the cell lines with either 2Gy ionising radiation, 20 µM Cisplatin, or 50 µM 5-fluorouracil (5-FU).
Project description:This SuperSeries is composed of the following subset Series: GSE15372: Expression data from A2780 (cisplatin-sensitive) and Round5 A2780 (cisplatin-resistant) cell lines. GSE15373: Promoter CpG island methylation data from A2780 (cisplatin-sensitive) and Round5 A2780 (cisplatin-resistant) cell lines. Refer to individual Series
Project description:One of the major challenges for chemotherapy is appearance of resistance to compounds. Despite several singling pathways have been implicated in development of Adriamycin (ADM) resistance, mechanisms involved in ADM-resistant osteosarcoma progression remain largely unknown. The present study attempts to illustrate the role of long noncoding RNA ARSR in development of ADM-resistance. We found lncRNA ARSR overexpressed in the Adriamycin resistant cell lines U2OS/ADM and MG63/ADM, accompanied with acquired multidrug resistance against to paclitaxel and cisplatin. Overexpression of lncRNA ARSR triggered rhodamine 123 efflux and survival, as well as migration of ADM resistant cells. Conversely, depletion of ARSR promoted rhodamine 123 retention and apoptosis while reduced motility of ADM resistant cells. Further investigation revealed that upregulation of ARSR enhanced Akt phosphorylation on Ser473 and increment of multidrug resistance-associated protein-1, apoptosis inhibitor Survivin and matrix metalloproteinase-2. Reduction of ARSR overcame the resistance to ADM and magnified the suppression of Akt-mediated signaling pathways by MK-2206. The current study gained novel evidence for understanding the mechanisms underlying adaptive ADM resistance, and provided rational to improve Akt-targeted therapy towards refractory osteosarcoma. Methods: The expression of lncRNA was analyzed by RT2 lncRNA PCR Arrays. The differential expressed lncRNAs were further verified by qRT-PCR. The relationship between lncRNA expression and clinical features was evaluated with Spearman correlation test. Cell proliferation was measured by MTT assay. Cell apoptosis percentage was detected by ANNEXIN V-PI analysis. The promoter activity was illustrated by Luciferase assay, and the change of microRNA and protein was detected by qRT-PCR and western blot, separately. Results: The expression of HAND2-AS1 declined in bladder cancer and correlated with depth of invasion and grades negatively. Restoration of HAND2-AS1 hampered cell growth by provoking cell apoptosis. Furthermore, one of the HAND2-AS1 sponge, miR-146, was found overexpression in bladder cancer tissue and cell lines. Expression of miR-146 related to HAND2-AS1 expression negatively. One of the targeted genes of miR-146, retinoic acid receptor beta (RARB) was downregulated in bladder cancer. In addition, the expression of RARB related to miR-146 negatively. Lost-of-function and gain-of-function experiments were used to identify the mechanisms underlying association of lncRNA HAND2-AS1: miR-146: RARB. miR-146 targeted RARB directly and hindered RARB-mediate apoptosis. However, the hindrance was impaired by HAND2-AS1 notably. Conclusion: HAND2-AS1 diminished miR-146 expression, thereby releasing the suppression of miR-146 on RARB-mediated apoptosis, promoting bladder cancer regression. Long noncoding RNA profiling by array