Long noncoding RNA TC0101441 induces epithelial–mesenchymal transition in epithelial ovarian cancer metastasis by downregulating KiSS1

Abstract

Peritoneal metastasis is a critical feature and clinical challenge in epithelial ovarian cancer (EOC). We previously identified a novel long noncoding RNA (lncRNA, TC0101441) in epithelial ovarian cancer (EOC) using microarrays. However, the impact of TC0101441 on EOC metastasis and prognosis remains unclear. TC0101441 expression in EOC tissues and its correlation with clinicopathological factors and prognosis were examined. A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of TC0101441 in EOC metastasis. We found that TC0101441 levels were elevated in EOC tissues compared with those in normal controls and significantly correlated with an advanced clinical stage and lymph node metastasis. TC0101441 was determined to be an independent prognostic predictor of overall survival (OS) and disease‐free survival (DFS). Furthermore, loss‐of‐function assays showed that TC0101441 promoted the invasive and metastatic capacities of EOC cells both in vitro and in vivo. Mechanistically, the prometastatic effects of TC0101441 were linked to the induction of epithelial–mesenchymal transition (EMT). Importantly, KiSS1 was identified as a downstream target gene of TC0101441 and was downregulated by TC0101441 in EOC cells. After TC0101441 was silenced, the corresponding phenotypes of EOC cell invasion and EMT were reversed by the overexpression of KiSS1. Taken together, our data suggest that TC0101441 functions as a potential promigratory/invasive oncogene by promoting EMT and metastasis in EOC through downregulation of KiSS1, which may represent a novel prognostic marker and therapeutic target in EOC.

RETRACTED: NEAT1 Overexpression Indicates a Poor Prognosis and Induces Chemotherapy Resistance via the miR-491-5p/SOX3 Signaling Pathway in Ovarian Cancer

“…Chemotherapy is widely used for treating locally advanced and metastatic OC in clinical settings; however, chemoresistance is inevitable during the long course of treatment, with the 5 years survival rate of OC patients limited to 40% ( Jiang et al, 2019 ). Due to lack of sensitive approaches for early diagnosis and the prevention of resistance to chemotherapy, most patients eventually succumb to recurrent, progressive cancers ( Qiu et al, 2019 ; Yang Y. et al, 2019 ). In consequence, the prevention, diagnosis and treatment may benefit from deeper knowledge of molecular mechanisms involved in ovarian carcinogenesis.…”

Silencing of the long noncoding RNA LINC01132 alleviates the oncogenicity of epithelial ovarian cancer by regulating the microRNA‑431‑5p/SOX9 axis

“…Multiple studies performed by different scientists have revealed the critical roles of lncRNAs in the oncogenicity of EOC. For instance, NORAD (31), LINC00673 (32) and Tc0101441 (33) were upregulated in EOc and have been identified as tumour promoters. Conversely, the low expression of WDFY3-AS2 (34), MAGI2-AS3 (35) and AOC4P (36) in EOc resulted in anti-tumourigenic effects.…”

Silencing of Long Noncoding RNA LINC01132 Alleviates the Oncogenicity of Epithelial Ovarian Cancer by Regulating the microRNA-431-5p/SOX9 Axis

“…Multiple studies performed by different scientists have revealed the critical roles of lncRNAs in the oncogenicity of EOC. For instance, NORAD [27], LINC00673 [28] and TC0101441 [29] are upregulated in EOC and identi ed as tumour promoters. In contrast, low expression of WDFY3-AS2 [30], MAGI2-AS3 [31] and AOC4P [32] in EOC results in antitumorigenic effects.…”