Small RNA Sequencing Identifies PIWI-Interacting RNAs Deregulated in Glioblastoma—piR-9491 and piR-12488 Reduce Tumor Cell Colonies In Vitro

Abstract

Glioblastoma (GBM) is the most frequently occurring primary malignant brain tumor of astrocytic origin. To change poor prognosis, it is necessary to deeply understand the molecular mechanisms of gliomagenesis and identify new potential biomarkers and therapeutic targets. PIWI-interacting RNAs (piRNAs) help in maintaining genome stability, and their deregulation has already been observed in many tumors. Recent studies suggest that these molecules could also play an important role in the glioma biology. To determine GBM-associated piRNAs, we performed small RNA sequencing analysis in the discovery set of 19 GBM and 11 non-tumor brain samples followed by TaqMan qRT-PCR analyses in the independent set of 77 GBM and 23 non-tumor patients. Obtained data were subsequently bioinformatically analyzed. Small RNA sequencing revealed 58 significantly deregulated piRNA molecules in GBM samples in comparison with non-tumor brain tissues. Deregulation of piR-1849, piR-9491, piR-12487, and piR-12488 was successfully confirmed in the independent groups of patients and controls (all p < 0.0001), and piR-9491 and piR-12488 reduced GBM cells’ ability to form colonies in vitro. In addition, piR-23231 was significantly associated with the overall survival of the GBM patients treated with Stupp regimen (p = 0.007). Our results suggest that piRNAs could be a novel promising diagnostic and prognostic biomarker in GBM potentially playing important roles in gliomagenesis.

The role of piRNAs in predicting and prognosing in cancer: a focus on piRNA-823 (a systematic review and meta-analysis)

“…Out of the 20 studies analyzed, four focused primarily on RCC [ 26 , 44 , 50 , 55 ], four on CRC [ 13 , 24 , 27 , 53 ], three on Head and neck squamous carcinoma (HNSCC) [ 48 , 49 , 54 ], two on Gastric cancer (GC) [ 46 , 47 ], one on Breast cancer (BC) [ 51 ], one on Diffuse large B cell lymphoma (DLBCL) [ 41 ], one on Ovarian cancer (OC) [ 42 ], one on Multiple myeloma (MM) [ 43 ], one on Glioblastoma (GBM) [ 45 ], one on NSCLC [ 25 ], and one on Hodgkin lymphoma (HL) [ 52 ].…”

“…Out of these 20 studies, nine records utilized high-throughput assays of RNA sequencing [ 13 , 45 , 47 – 49 , 51 , 53 – 55 ], seven used qRT-PCR [ 24 – 26 , 43 , 46 , 50 , 52 ], three used Microarray analysis [ 27 , 41 , 44 ], and one used ISH [ 42 ] for quantification of piRNAs in patients biological specimen. The majority of these studies were conducted in China (nine studies) [ 13 , 24 , 25 , 27 , 41 – 43 , 46 , 55 ], three studies followed by the USA [ 48 , 49 , 53 ], three in Canada [ 47 , 51 , 54 ], two in Czech Republic [ 26 , 45 ], two in Germany [ 44 , 50 ], and one in Spain [ 52 ].…”

“…The biological samples collected for analysis included serum ( n = 5) [ 13 , 24 , 26 , 43 , 50 ], tissue ( n = 11) [ 24 – 27 , 47 – 50 , 53 – 55 ], Formalin-Fixed Paraffin-Embedded (FFPE) samples ( n = 4) [ 41 , 42 , 51 , 52 ], blood samples ( n = 1) [ 43 ], fresh-frozen tissues ( n = 2) [ 44 , 45 ], gastric juice samples ( n = 1) [ 46 ], bone marrow aspirates ( n = 1) [ 43 ], and urine samples ( n = 1) [ 26 ].…”

PIWI-interacting RNA-17458 is oncogenic and a potential therapeutic target in cervical cancer

“…It has been shown that piRNA-36712 was low expressed in breast cancer than in matched controls and its overexpression restrains progression and chemoresistance of CC cells by interacting with SEPW1P RNAs 21 . By piRNA expression profile analysis, Bartos et al report that piRNA-9491 and piRNA-12488 were significantly dysregulated in glioblastoma cells and could reduce the ability to form colonies in vitro 17 . Here, we showed that piRNA-17458 was significantly overexpressed in CC tissues and cells when compared with that in matched controls.…”

Delivering the Promise of Gene Therapy with Nanomedicines in Treating Central Nervous System Diseases

“…Recently several piRNA (e.g., piR‐9491 and piR‐2488) have also been identified to be associated with GBM disease development. [ 256 ] Regardless, up to date, no specific gene therapy targeting piRNA for CNS diseases has been demonstrated. Most of the works still focus on discovering the piRNA as the current stage.…”