Identification of miR-145 targets through an integrated omics analysis

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and protein synthesis. To characterize functions of miRNAs and to assess their potential applications, we carried out an integrated multi-omics analysis to study miR-145, a miRNA that has been shown to suppress tumor growth. We employed gene expression profiling, miRNA profiling and quantitative proteomic analysis of a pancreatic cancer cell line. In our transcriptomic analysis, overexpression of miR-145 was found to suppress the expression of genes that are implicated in development of cancer such as ITGA11 and MAGEA4 in addition to previously described targets such as FSCN1, YES1 and PODXL. Based on miRNA profiling, overexpression of miR-145 also upregulated other miRNAs including miR-124, miR-133b and miR-125a-3p, all of which are implicated in suppression of tumors and are generally co-regulated with miR-145 in other cancers. Using the SILAC system, we identified miR-145-induced downregulation of several oncoproteins/cancer biomarkers including SET, RPA1, MCM2, ABCC1, SPTBN1 and SPTLC1. Luciferase assay validation carried out on a subset of downregulated candidate targets confirmed them to be novel direct targets of miR-145. Overall, this multi-omics approach provided insights into miR-145-mediated tumor suppression and could be used as a general strategy to study the targets of individual miRNAs.

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.…”

Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation

“…In addition, proteome, transcriptome and miRNome data identified networks related to cardiotoxicity in human pluripotent stem cells 49 . In this manner, miR-145 targets were identified in pancreatic cancer 50 and several putative miRNA targets were found in intestinal cell lines 51 . Furthermore, a crosstalk between proteome and non-coding RNAs was proposed by proteome and miRNome data during ongoing endothelial senescence 52 and during telomere shortening in cancer cells 53 .…”

MicroRNA Targeted Therapeutic Approach for Pancreatic Cancer

“…In addition, miR-145 could also target pluripotency maintenance factors such as OCT4, SOX2, NANOG, and KLF4 (Figure 1 ) 68 . Enforced expression of miR-145 (transfecting cells with pre-miR-145) reduced the expression levels of cancer related genes including ITGA11, MAGEA4, SET, RPA1, MCM2, ABCC1, SPTBN1 and SPTLC1 69 . All of these miR-145 target genes are critical for pancreatic carcinogenesis, stemness maintenance, and growth of pancreatic cancer.…”