Pseudogene HSPB1P1 contributes to renal cell carcinoma proliferation and metastasis by targeting miR‐296‐5p to regulate HMGA1 expression

Abstract

With the aid of next‐generation sequencing technology, pseudogenes have been widely recognized as functional regulators in the development and progression of certain diseases, especially cancer. Our present study aimed to investigate the functions and molecular mechanisms of HSPB1‐associated protein 1 pseudogene 1 (HSPB1P1) in renal cell carcinoma (RCC). HSPB1P1 expression at the mRNA levels was determined by quantitative real‐time polymerase chain reaction, and its clinical significance was assessed. Cell viability was detected by Cell Counting Kit‐8 assay. Cell migration and invasion were detected by transwell assays. The location of HSPB1P1 in RCC cells was detected by subcellular distribution analysis. The direct relationship between HSPB1P1 and miR‐296‐5p/HMGA1 axis was verified by dual‐luciferase reporter assay and RNA immunoprecipitation assay. Our results identify the elevated expression of HSPB1P1 in RCC tissues and cell lines, which predicted advanced progression and poor prognosis in patients with RCC. Knockdown of HSPB1P1 suppressed cell proliferation, migration, and invasion, and reversed epithelial–mesenchymal transition process in RCC. HSPB1P1 was mostly enriched in the cytoplasm and functioned as a miRNA sponge for miR‐296‐5p and then regulated high‐mobility group A1 expression. In conclusion, our study indicated that HSPB1P1 contributed to RCC progression by targeting the miR‐296‐5p/HMGA1 axis, and should be considered as a promising biomarker and therapeutic target for clinical applications.

DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis

“…Another gene, PLEKHB2 (also called evectin-2), negatively correlated with the DLK2 level, plays a critical role in the YAP oncogenic pathway of proliferating cells [68], and it is also downregulated in colon cancer [69]. In the miRNA analysis, the expressions of miR-296, miR-331, and miR-28 targets (possible oncogenes) were positively correlated with the DLK2 level, and previous studies indicate that miR-296, miR-331, and miR-28 sever as tumor suppressors [70][71][72]. Furthermore, the DLK2 level was negatively correlated with the expressions of miR-496 and miR-373 targets (possible tumor suppressor genes).…”

Novel circular RNAs of the apoptosis‐related BAX and BCL2L12 genes identified in a chronic lymphocytic leukemia cell line using nanopore sequencing

“…Moreover, the two most frequently detected BAX circRNAs in EHEB are predicted to sponge miR‐296‐5p. This miRNA has been characterized as a tumor suppressor in several malignancies and its upregulation can induce apoptosis [ 46 , 47 , 48 ]. Last but not least, circ‐BAX‐4 is predicted to sponge miR‐378a‐3p, the expression levels of which are lower in CLL patients, compared to normal individuals.…”

A key regulatory loop AK4P1/miR-375/SP1 in pancreatic adenocarcinoma

“…As a type of noncoding RNA, pseudogene-derived RNA could exert its effects through competitively binding to shared miRNAs [ 15 , 16 ]. To ascertain if AK4P1 functions by this way in pancreatic adenocarcinoma, first of all, lncLocator tool was used to predict the subcellular location of AK4P1 as previously described [ 17 ].…”