Decreased expression of long non-coding RNA GAS5 promotes cell proliferation, migration and invasion, and indicates a poor prognosis in ovarian cancer

Abstract

Long non-coding RNA growth arrest-specific 5 (GAS5) was reported to be aberrantly expressed in various types of cancers. However, the role of GAS5 in the evolution and progression of ovarian cancer remains elusive. In the present study, we aimed to investigate the cellular function and clinical significance of GAS5 in ovarian cancer. GAS5 expression levels in 63 ovarian cancer tissues were detected by quantitative real-time PCR. Cell Counting Kit-8 (CCK-8) assay was performed to analyze the effect of GAS5 on cell proliferation. The effect of GAS5 on cell migration and invasion was detected using Transwell assay. Cell apoptosis was evaluated by flow cytometry and Hoechst staining. SKOV3 cells with stable expression of GAS5 were injected into nude mice to study the effect of GAS5 on tumorigenesis in vivo. Western blotting was used to determine the protein levels of GAS5 potential targets. The results showed that GAS5 was markedly decreased in tumor tissues and a lower expression of GAS5 was detected in tumors with larger size, deeper invasive depth and higher tumor stage. Patients with low GAS5 expression level had poorer disease-free (P<0.0001) and overall survival (P=0.0016) than those with high GAS5 expression. Moreover, overexpression of GAS5 was demonstrated to suppress ovarian cancer cell proliferation in vitro and in vivo. Finally, we found that GAS5 influenced ovarian cancer cell proliferation, partly via regulating cyclin D1, p21 and apoptosis protease activating factor 1 (APAF1) expression. Our findings suggest that lncRNA GAS5 may represent a novel indicator of poor prognosis in ovarian cancer and may be a potential therapeutic target for diagnosis and therapy.

LncRNA GAS5 suppresses the tumorigenesis of cervical cancer by downregulating miR-196a and miR-205

“…26 In ovarian cancer, GAS5 was decreased in tumor tissues and indicated a poor prognosis; moreover, overexpression of GAS5 inhibited ovarian cancer cell proliferation partly via regulating cyclin D1, p21, and apoptosis protease activating factor 1 (APAF1) expression. 27 In colorectal cancer (CRC), GAS5 was commonly downregulated in CRC tissues, serum of patients, and CRC cell lines; knockdown of GAS5 promoted cell proliferation and colony formation while overexpression of GAS5 exhibited the opposite results. 28 In hepatocellular carcinoma, low expression of GAS5 indicated a poor prognosis and promoted cell proliferation, invasion, and suppressed apoptosis by negatively regulating vimentin.…”

Long Non-Coding RNAs: the New Horizon of Gene Regulation in Ovarian Cancer

“…Further inhibition of BC200 enhances the proliferative capacity of cancer cells in vivo [60], and overexpression of GAS5 offsets the aggressive behavior of OC cells both in vitro and in vivo [61]. Subsequent experiments revealed that GAS5 contributes to OC tumorigenesis through downstream effects on genes related to cell cycle progression, namely, CDKN1A, cyclin D1, and apoptotic protease-activating factor (APAFA).…”

“…Reduced expression of brain cytoplasmic RNA 200 (BC200; also known as brain cytoplasmic RNA1) and growth arrest-specific 5 (GAS5) has been observed in ovarian tumor tissues and cell lines [60,61]. Further inhibition of BC200 enhances the proliferative capacity of cancer cells in vivo [60], and overexpression of GAS5 offsets the aggressive behavior of OC cells both in vitro and in vivo [61].…”

“…For example, poor prognosis (shorter OS) is associated with high expression of nuclear paraspeckle assembly transcript 1 (NEAT1) [79], ANRIL [63], and AB0736614 in patients with OC [69]. Furthermore, both shorter OS and disease-free survival (DFS) were associated with up-regulated CCAT2 [62] and HOXA11as [66], whereas low expression of GAS5 was associated with shorter OS and DFS in patients with OC [61]. Another lncRNA, SPRY4-IT1, was found to be highly expressed in OC and could be used as an independent prognostic agent for OS and PFS, and a diagnostic marker for tumors in patients with OC [67].…”

Analysis of long non-coding RNA expression profiles in ovarian cancer

“…Hence, identifying novel targets that could serve as biomarkers for early diagnosis and treatment of ovarian cancer is urgently required. Previous studies investigating effective early ovarian cancer diagnostic markers have revealed that the development of ovarian cancer is associated with the aberrant expression of specific lncRNAs, including GAS5 (21), SPRY4-IT1 (22), C17orf91 (23) and CCAT2 (24). …”