Long non-coding RNA CHCHD4P4 promotes epithelial-mesenchymal transition and inhibits cell proliferation in calcium oxalate-induced kidney damage

Abstract

Kidney stone disease is a major cause of chronic renal insufficiency. The role of long non-coding RNAs (lncRNAs) in calcium oxalate-induced kidney damage is unclear. Therefore, we aimed to explore the roles of lncRNAs in glyoxylate-exposed and healthy mouse kidneys using microarray technology and bioinformatics analyses. A total 376 mouse lncRNAs were differentially expressed between the two groups. Using BLAST, 15 lncRNA homologs, including AU015836 and CHCHD4P4, were identified in mice and humans. The AU015836 expression in mice exposed to glyoxylate and the CHCHD4P4 expression in human proximal tubular epithelial (HK-2) cells exposed to calcium oxalate monohydrate were analyzed, and both lncRNAs were found to be upregulated in response to calcium oxalate. To further evaluate the effects of CHCHD4P4 on the cell behavior, we constructed stable CHCHD4P4-overexpressing and CHCHD4P4-knockdown HK-2 cells. The results showed that CHCHD4P4 inhibited cell proliferation and promoted the epithelial-mesenchymal transition in kidney damage and fibrosis caused by calcium oxalate crystallization and deposition. The silencing of CHCHD4P4 reduced the kidney damage and fibrosis and may thus be a potential molecular target for the treatment of kidney stones.

LncRNA HOXA11‐AS regulates calcium oxalate crystal–induced renal inflammation via miR‐124‐3p/MCP‐1

“…Over the past decade, LncRNAs, which are members of the noncoding RNA family, have been well‐accepted as crucial biological RNAs in a wide variety of cancerous and noncancerous diseases rather than transcriptional ‘noise’ or cloning artefacts . In a previous study, we identified several CaOx stone‐related lncRNAs using a microarray technique and demonstrated that lncRNA CHCHD4P4 promoted renal EMT in CaOx nephrolithiasis . Another lncRNA, HOXA11‐AS, has been found to have multiple biological functions in a great deal of diseases in recent years .…”

LncNEN885 inhibits epithelial‐mesenchymal transition by partially regulation of Wnt/β‐catenin signalling in gastroenteropancreatic neuroendocrine neoplasms

“…In recent years, lncRNAs have been a hot point in the research of developmental processes and disease states as a potentially novel and crucial layer of biological regulation . Several studies have reported that dysregulation of lncRNAs might induce multiple diseases, such as diabetes, kidney dysfunction, cardiovascular diseases, and malignant tumors . The role of lncRNAs in cancer has been the focus of this research .…”

“…19 Several studies have reported that dysregulation of lncRNAs might induce multiple diseases, such as diabetes, kidney dysfunction, cardiovascular diseases, and malignant tumors. [20][21][22][23] The role of lncRNAs in cancer has been the focus of this research. 24 However, little is known about the role of lncRNAs in GEP-NENs.…”

Increased expression of long noncoding RNA GAS6‐AS2 promotes proliferation and inhibits apoptosis of melanoma cells via upregulating GAS6 expression

“…Increasing evidences have found that many lncRNAs are aberrantly expressed in various diseases including cancers . Furthermore, functional studies of lncRNAs have highlighted the fact that many lncRNAs have crucial roles in a diverse array of diseases including cancers …”

“…[15][16][17][18][19] Furthermore, functional studies of lncRNAs have highlighted the fact that many lncRNAs have crucial roles in a diverse array of diseases including cancers. [20][21][22][23] As to melanoma, several lncRNAs are reported to have functional significances. LncRNA H19 was revealed to promote glucose metabolism and cell growth in melanoma.…”