Suppressed expression of long non-coding RNA HOTAIR inhibits proliferation and tumourigenicity of renal carcinoma cells

Abstract

Although long non-coding RNAs (lncRNAs) are known to play an important role in cell regulation in several cancers, the regulatory mechanisms in renal carcinoma cells remain unclear. HOX transcript antisense RNA (HOTAIR), an lncRNA, coordinates with chromatin-modifying enzymes to regulate gene silencing. HOTAIR is over-expressed in several types of carcinoma cells. Thus, we hypothesised that lncRNA HOTAIR is crucial for cell proliferation and invasion and that its knockdown induces apoptosis in renal carcinoma cells. lncRNA HOTAIR expression was found to be elevated in renal carcinoma cells. Additionally, lncRNA HOTAIR knockdown by RNA interference with siRNA was found to significantly affect the cell cycle in the G0/G1 phase and weaken the abilities of cell proliferation and invasion in vitro. Xenograft experiments confirmed that the growth of xenograft tumours formed by renal carcinoma cells was suppressed after silencing lncRNA HOTAIR expression. Moreover, chromatin immunoprecipitation (ChIP) and RNA-binding protein immunoprecipitation (RIP) assays revealed that knockdown of lncRNA HOTAIR led to the weakening of the recruitment and binding abilities of EZH2 and H3K27me3 locus with lncRNA HOTAIR. Furthermore, the cell cycle-related gene locus was in an active transcriptional state by the silencing of lncRNA HOTAIR expression and modulation of covalent histones.

Genetic polymorphisms of HOTAIR gene are associated with the risk of breast cancer in a sample of southeast Iranian population

“…HOTAIR overexpression is associated with tumor invasion, progression, metastasis, and poor prognosis of corresponding cancers. 13,14 HOTAIR gene, a 2158 nucleotides in length lncRNA, is transcribed from the HOXC locus located on chromosome 12q13.13 15 and has an important role in gene regulation via the alternation of chromatin structure (histone modifications). 15,16 Several studies investigated the impact of HOTAIR gene polymorphisms on the incidence risk of various cancers including BC, gastric cancer, prostate cancer, and ovarian cancer.…”

Long Non-Coding RNA Emergence During Renal Cell Carcinoma Tumorigenesis

“…LncRNA HOTAIR knockdown by RNA interference with siRNA significantly affects the G0/G1 phase cell cycle and weakens RCC cell proliferation [26], which is suppressed by miR-141 in an Ago2-dependent manner [77]. LncRNA SASC2 is also downregulated by miR-21 to increase the proliferation of RCC.…”

“…Below, we first describe the roles and molecular mechanisms that underlie lncRNAs involved in RCC including lncRNA TUG1 [22], H19 [23], MEG3 [24], KCQN1OT1 [17], MALAT1 [25], HOTAIR [26], and others. We then discuss the potential clinical application of lncRNAs in RCC diagnosis and treatment.…”

Noncoding RNAs: New Players in Cancers

“…In contrast, tumor suppressor lncRNAs with downregulated expression patterns in cancer include lincRNA-p21, Gas5, PTENP1, and lncRNA-LET (lncRNA low expression in tumor). For example, the high expression of HOTAIR with a pro-tumor effect has been implicated in various tumor types, including breast cancer [ 228 ], liver cancer [ 229 ], colorectal carcinoma [ 185 ], gastrointestinal stromal tumor [ 230 ], pancreatic cancer [ 231 ], non-small cell lung carcinoma (NSCLC) [ 232 ], nasopharyngeal carcinoma [ 233 ], laryngeal squamous cell carcinoma (LSCC) [ 234 ], esophageal squamous cell carcinoma (ESCC) [ 235 ], urothelial carcinoma [ 236 ], ovarian cancer [ 237 ], renal carcinoma [ 238 ], gall bladder cancer [ 239 ], nonfunctional pituitary adenoma [ 240 ], PCa [ 241 ], melanoma [ 242 ], and endometrial tumors [ 243 ].…”