lncRNA HEIH accelerates cell proliferation and inhibits cell senescence by targeting miR-3619-5p/CTTNBP2 axis in ovarian cancer

Abstract

Objective: Epithelial ovarian cancer is the most lethal malignancy in gynecology. Numerous studies have confirmed that long noncoding RNAs (lncRNAs) are abnormally expressed in ovarian cancer and are closely associated with the cell proliferation and senescence in cancers. However, the role and underlying molecular mechanism of long noncoding RNA high expression in hepatocellular carcinoma (HEIH) in ovarian cancer remain unknown. Methods: Experiments including Real-time quantitative polymerase chain reaction, RNA immunoprecipitation, luciferase reporter, Fluorescence in situ hybridization, western blot, colony formation assays, β-galactosidase senescence assay, cell apoptosis, proliferation, invasion, and migration assays were applied to investigate the role of HEIH in ovarian cancer. The data were expressed as the mean ± standard deviation. Student t test was used to compare the data between two groups. The one-way analysis of variance was applied to compare the data among multiple groups with Tukey post hoc test. All experiments were repeated three times. P < 0.05 was considered statistically significant. Results: Herein, HEIH expression was found to be up-regulated in ovarian cancer tissues (n = 25; twofold higher than normal tissues, P < 0.05) and cell lines (sixfold higher than normal ovarian epithelial cell line on average, P < 0.05), and high HEIH expression predicted poor prognosis (survival rate is about 25% after 40 mo; P < 0.05). Moreover, we found that HEIH accelerated proliferation, migration, and invasion, whereas inhibited cell senescence in ovarian cancer (P < 0.05). In mechanism, HEIH was confirmed to serve as a sponge for miR-3619-5p, and miR-3619-5p counteracted HEIH-mediated regulation of ovarian cancer (P < 0.05). Besides, cortactin-binding protein 2 (CTTNBP2) was found to be the downstream target of miR-3619-5p. Rescue assays validated that CTTNBP2 up-regulation significantly reversed the inhibitory effects of HEIH knockdown on ovarian cancer progression (P < 0.05). Furthermore, we found that HEIH facilitated tumor growth in vivo by regulating CTTNBP2 expression (P < 0.05). Conclusions: In conclusion, our research revealed that HEIH accelerated cell proliferation, migration and invasion, whereas inhibited cell senescence in ovarian cancer via targeting the miR-3619-5p/CTTNBP2 axis. These findings may be valuable for finding new therapeutic targets to improve ovarian cancer treatment.

High Expression of lncRNA HEIH is Helpful in the Diagnosis of Non-Small Cell Lung Cancer and Predicts Poor Prognosis

“…These results suggest that high expression of lncRNA HEIH predicts poor prognosis in patients with NSCLC. The expression of HEIH is up-regulated in ovarian cancer tissues and cell lines, and high expression of HEIH indicates a poor prognosis [25]. Oesophageal squamous cell carcinoma patients with high lncRNA HEIH expression have poorer prognosis than those with low expression [26].…”

Long non-coding RNA HEIH: a novel tumor activator in multiple cancers

“…Besides, elevated HEIH expression was related to poor prognosis. Mechanically, HEIH accelerated cell proliferation, migration and invasion, whereas inhibited cell senescence via targeting the miR-3619-5p/CTTNBP2 axis [ 44 ]. It is tempting to conclude that bias towards up-regulation of HEIH in cancer may results from the above large-scale practice discovering HEIH from various cancer samples.…”

“…Coherently with this function, HEIH was found to promote malignant phenotypes by competitively binding miR-4458 to upregulate the expression of SOCS1and PBX3 in breast cancer and esophageal cancer, respectively [ 33 , 51 ]. Similarly, HEIH triggered ovarian cancer and tongue squamous cell carcinoma development by sponging miR-3619-5p, and consequently upregulating the miR-3619-5p targets CTTNBP2 and HDGF [ 28 , 44 ]. Nafea et al and Cui et al showed HEIH could directly interact with miR-939 to counteract the effects of miR-939 on the transcription of Bcl-xl in colorectal cancer [ 64 ] and the production of NO 2 in TNBC [ 52 ].…”

“…The increased expression of HEIH promoted tumor development and is strongly correlated with clinicopathological parameters, including lymph node metastasis, as well as tumor size, differentiation, clinical stage and recurrence, and thus could be used as a prognostic marker for several cancers listed in Table 1 . Notably, Kaplan–Meier analysis indicated a negative correlation between HEIH expression levels and overall survival rates in patients with breast cancer, OC and retinoblastoma [ 44 , 48 , 57 ]. Jointly, the above findings indicate that HEIH might represent an independent parameter for predicting prognosis in various cancers, although further large trials are still required for confirmation.…”

A Combined Long Noncoding RNA Signature as a Candidate Prognostic Biomarker for Ovarian Cancer

“…Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs with a length of more than 200 nucleotides. Several lncRNAs have been confirmed to be deregulated and act as critical regulators in OC ( 4 ). Overexpression of lncRNA HOTTIP promoted the growth and metastasis of OC via the miR-615-3p/SMARCE1 axis ( 5 ).…”