Both inhibition and enhanced expression of miR‐31 lead to reduced migration and invasion of pancreatic cancer cells

Abstract

MicroRNAs (miRNAs) are short single-stranded RNA molecules that have a critical role in the regulation of gene expression. Alterations in miRNA expression levels have been observed in multiple tumor types and there is clear evidence on their active involvement in cancer development. Here, a comprehensive miRNA expression profiling in 16 pancreatic cancer cell lines and four normal pancreatic samples provided a specific molecular signature for pancreatic cancer and enabled us to identify 72 differentially expressed miRNAs with approximately half of them being up- and half downregulated in cancer cells as compared with normal samples. Of these, miR-31 was selected for further functional analyses based on its interesting "on-off" type expression profile, i.e., very low or even absent expression in normal pancreas and in six of the pancreatic cancer samples but extremely high expression in the remaining 10 cell lines. Quite unexpectedly, both the inhibition of miR-31 in AsPC-1 and HPAF-II pancreatic cancer cells with high endogenous expression and forced expression of miR-31 in MIA PaCa-2 with low endogenous levels led to reduced cell proliferation, migration, and invasion. More importantly, in AsPC-1 cells further enhancement of miR-31 also resulted in reduced cell migration and invasion, implicating that the level of miR-31 is critical for these phenotypes. This study highlights a specific miRNA expression pattern in pancreatic cancer and reveals that manipulation of miR-31 expression leads to reduced cell migration and invasion in pancreatic cancer.

Transcriptional Regulation of miR-31 by Oncogenic KRAS Mediates Metastatic Phenotypes by Repressing RASA1

“…On one hand, miR-31 is found up regulated and to enhance invasion migration in 6 cancer types (cervical, colorectal, cutaneous squamous cell, esophageal squamous cell, Kaposi’s sarcoma, lung) and on the other hand, is found down regulated and to repress invasion migration in 7 cancer types (breast, esophageal, Ewing sarcoma, glioma, melanoma, ovarian, prostate). A previous report of the role of miR-31 in pancreatic cancer is ambiguous; both inhibition and enforced expression of miR-31 reduced migration and invasion in PDAC cell lines (35). In the present study, the enforced expression of miR-31 enhanced invasion and migration in three pancreatic cancer cell lines tested irrespective of KRAS mutational status.…”

Transcriptome Profiling of Panc-1 Spheroid Cells with Pancreatic Cancer Stem Cells Properties Cultured by a Novel 3D Semi-Solid System

“…5C). Among them, miR-21, miR-31-3p, miR-203, miR-16 were up-regulated which were found to be engaged in regulating apoptosis (miR-21) [31], migration and invasion (miR-31 and miR-203) [32,33], and diagnosis(miR-16) [34] of pancreatic cancer. On the other hand, miR-210-3p, miR-29a, miR-125b, miR-133a were down-regulated, they have been reported to be associated with pancreatic cancer such as regulating cells interaction (miR-210) [35], as an autophagy inhibitor (miR-29a) [36], as a tumor suppressor(miR-125b and miR-133a) [36].…”

MicroRNAs and head and neck cancer: Reviewing the first decade of research

“…It has also been observed to be upregulated in hepatocellular carcinoma and colorectal cancer but downregulated in breast, prostate and ovarian cancer [100][101][102][103][104][105]. In pancreatic cancer under and over-expression of miR-31 lead to inhibited migration and invasion in different cell lines, dependent on their endogenous levels of miR-31 [106]. As mentioned earlier miR-31 activates the HIF pathway suggesting an important role in the development of HNSCC, however upregulation of miR-31 in breast cancer models causes [107].…”