Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL

Abstract

Abstract.Metastasis is the main cause of cancer-associated death, and metastasis of pancreatic cancer remains difficult to treat because of its aggressiveness. MicroRNAs (miRNAs) play crucial roles in the regulation of various human transcripts, and many miRNAs have been reported to correlate with cancer metastasis. We identified an anti-metastatic miRNA, miR-5100, by investigating differences in miRNA profiling between highly metastatic pancreatic cancer cells and their parental cells. Overexpression of miR-5100 inhibited colony formation (P<0.05), cell migration (P<0.0001) and invasion (P<0.0001) of pancreatic cancer cells. In addition, we identified a possible target of miR-5100, podocalyxin-like 1 (PODXL), and demonstrated miR-5100 directly binds to the 3' untranslated region of PODXL and post-transcriptionally regulates its expression in pancreatic cancer cells. Silencing PODXL resulted in diminished cell migration (P<0.0001) and invasion (P<0.05). We also clarified the close relationship between expression of PODXL in human pancreatic cancer specimens and liver metastasis (P= 0.0003), and determined that post-operative survival was longer in the low-PODXL expression group than in the high-PODXL expression group (P<0.05). These results indicate that miR-5100 and PODXL have considerable therapeutic potential for anti-metastatic therapy and could be potential indicators for cancer metastases in patients with pancreatic cancer.

miR-509-3-5P inhibits the invasion and lymphatic metastasis by targeting PODXL and serves as a novel prognostic indicator for gastric cancer

“…Moreover, some studies verified that overexpression of PODXL was correlated strongly with advanced clinicopathological features (poor differentiation, advanced tumor stage etc.) and poor prognosis [18–20, 35–37]. In our current study, we confirmed that PODXL was overexpressed in GC tissues based on the results of qRT-PCR, IHC and the database of TCGA.…”

“…However, it is undeniable that some others binding sites are existed in 3′UTR of PODXL, For instance, miR-5100, miR-199b-5P are treated as negative regulators of PODXL in pancreatic cancer [35] and acute myeloid leukemia [40]. Thus, we could not exclude the possibility that these miRNAs would be implicated in the regulation of PODXL expression in the progression of GC.…”

A Direct Podocalyxin–Dynamin-2 Interaction Regulates Cytoskeletal Dynamics to Promote Migration and Metastasis in Pancreatic Cancer Cells

“…Although typically absent in normal pancreas and nonmalignant pancreatic epithelial cells, approximately 30% to 69% of pancreatic ductal adenocarcinomas (PDAC) express PODXL, with the strongest expression exhibited by the invasive front of primary tumors (12,21,22). Moreover, high PODXL expression is associated with poor clinicopathologic characteristics and the development of distant metastasis (23,24). PODXL has also been shown to be an independent predictor of poor prognosis and is linked to higher risk of death and reduced survival (10,(22)(23)(24).…”

Podocalyxin‐like protein promotes gastric cancer progression through interacting with RUN and FYVE domain containing 1 protein

“…PODXL overexpression induced the EMT of lung adenocarcinoma cells via the PI3K pathway and contributed to tumor progression . As a target gene of miRNA, PODXL functions as a critical factor in the formation of primary tumors and distant tumor metastasis, for example, in testicular cancer, acute myeloid leukemia and pancreatic cancer …”

“…20 As a target gene of miRNA, PODXL functions as a critical factor in the formation of primary tumors and distant tumor metastasis, for example, in testicular cancer, acute myeloid leukemia and pancreatic cancer. [33][34][35][36] A study employing tissue microarrays and 2 antibodies (HPA2110 and HES9) to evaluate PODXL expression in GC tumors from 337 patients demonstrated the prognostic role of PODXL in GC. 22 Similarly, a study of 174 patients with esophageal or gastric adenocarcinoma revealed that PODXL expression was an independent prognostic biomarker for reduced time to recurrence and poor OS.…”