A new tumor suppressor lncRNA RP11-190D6.2 inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells

Abstract

At present, a large number of long noncoding RNAs (lncRNAs) from the human genome have been discovered. Meanwhile, emerging evidence has indicated that lncRNAs could play a critical role in the regulation of cellular processes such as cancer progression and metastasis. However, the functions of some new lncRNAs in the complex transcriptional process are mostly unknown at present. Existing studies suggest that loss of WW domain-containing oxidoreductase (WWOX) expression is linked with poor prognosis in numerous cancers, including epithelial ovarian cancer (EOC). However, the functional role of its antisense transcript RP11-190D6.2 is not clear to date. In this study, WWOX antisense transcript RP11-190D6.2 was analyzed specifically in EOC cells using real-time polymerase chain reaction and gain-/loss-of-function studies. We found that RP11-190D6.2 expression was positively correlated with WWOX expression. The RP11-190D6.2 expression was markedly downregulated in tumor tissues compared with normal tissues, but the RP11-190D6.2 expression was significantly downregu-lated in four EOC cell lines compared with human ovarian surface epithelial cell line. RP11-190D6.2 overexpression resulted in the increase of WWOX expression, whereas its knockdown led to the decrease of WWOX expression. We also found that RP11-190D6.2 was restored by 5-aza-2′-deoxycytidine treatment in EOC. In addition, the RP11-190D6.2 overexpression and knockdown experiments revealed that RP11-190D6.2 overexpression inhibited proliferation, migration, and invasion abilities in HO8910-PM cells, whereas RP11-190D6.2 knockdown in HEY-A8 cells had the opposite effect. The analyses in EOC implicate that RP11-190D6.2 may play a pivotal role in the regulation of tumor metastasis, suggesting that RP11-190D6.2 may serve as a potential biomarker and therapeutic target for EOC.

RETRACTED ARTICLE: Long non-coding RNA CCAT1 promotes multiple myeloma progression by acting as a molecular sponge of miR-181a-5p to modulate HOXA1 expression

“…For example, Cho et al reported that lncRNA-MALAT1 was overexpressed in patients with multiple myeloma and may serve as a molecular predictor of early progression [14]. Moreover, LncRNAs could function as oncogenes or tumor suppressors in different types of tumors depending on the circumstance [15][16][17][18].…”

The Role of Circulating Biomarkers in the Early Diagnosis of Ovarian Cancer

“…showed that a lncRNA named RP11-190D6.2 regulates the WW domain-containing oxidoreductase (WWOX) expression by acting like an antisense transcript of this gene [55]. WWOX is linked with poor prognosis in several cancers, including EOC [56].…”

“…WWOX is linked with poor prognosis in several cancers, including EOC [56]. In addition, RP11-190D6.2 appears to play a role in the regulation of tumor metastasis, thus it can be counted as a potential biomarker and therapeutic target for EOC [55]. Zhou et al compared several lncRNA expression profiles in a large number of OvCa patients from TCGA and found an eight-lncRNA signature predictive of overall survival [57].…”

Long noncoding RNA profiling revealed differentially expressed lncRNAs associated with disease activity in PBMCs from patients with rheumatoid arthritis

“…In recent years, lncRNAs have begun to receive substantial attention in the molecular biology field. Increasing evidence indicates that lncRNAs, as an versatile molecules that interact with RNA, DNA, or proteins to promote or restrain the expression of protein-coding genes, are involved in diverse biological processes, including cell proliferation, differentiation, apoptosis, and development[ 3 – 5 ]. Moreover, in the field of immunology, various studies have indicated that lncRNAs not only are emerging as important regulators of inflammatory gene expression in innate immune system[ 6 , 7 ], but also play a crucial role in directing the development and apoptosis of diverse immune cells and controlling the dynamic transcriptional programs that are hallmarks of immune cells activation or differentiation in adaptive immune system[ 8 – 11 ].…”