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

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.

Qiu JJ ，Lin XJ ，Tang XY ，Zheng TT ，Zhang XY ，Hua KQ ... -  《-》

Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer.

Although long non-coding RNAs (lncRNAs) are emerging as new regulators in the cancer paradigm, the involvement of lncRNAs in epithelial ovarian cancer (EOC) is just beginning to be studied. In this study, we focused on lncRNA HOX transcript antisense RNA (HOTAIR) and investigated its expression pattern, clinical significance, and biological function in EOC. HOTAIR expression in EOC tissues was examined and its correlation with clinicopathological factors and patient prognosis was analyzed. A series of in vitro and in vivo assays were performed to understand the role of HOTAIR in EOC metastasis. HOTAIR expression was elevated in EOC tissues, and HOTAIR levels were highly positively correlated with the FIGO stage, the histological grade of the tumor, lymph node metastasis, and reduced overall survival (OS) and disease-free survival (DFS). A multivariate analysis showed that HOTAIR expression is an independent prognostic factor of OS and DFS in patients with EOC. Additionally, the results of in vitro assays showed that the suppression of HOTAIR expression in the three highly metastatic EOC cell lines (SKOV3.ip1, HO8910-PM, and HEY-A8) significantly reduced cell migration/invasion. The results of in vivo assays further confirmed the pro-metastatic effects of HOTAIR. Moreover, the pro-metastatic effects of HOTAIR were partially mediated by the regulation of certain matrix metalloproteinases (MMPs) and epithelial-to-mesenchymal transition (EMT)-related genes. Our data suggest that HOTAIR plays a vital role in EOC metastasis and could represent a novel prognostic marker and potential therapeutic target in patients with EOC.

Qiu JJ ，Lin YY ，Ye LC ，Ding JX ，Feng WW ，Jin HY ，Zhang Y ，Li Q ，Hua KQ ... -  《-》

Upregulation of lncRNA AB073614 functions as a predictor of epithelial ovarian cancer prognosis and promotes tumor growth in vitro and in vivo.

Zeng S ，Liu S ，Feng J ，Gao J ，Xue F ... -  《-》

Long non-coding RNA AOC4P suppresses epithelial ovarian cancer metastasis by regulating epithelial-mesenchymal transition.

Lin X ，Tang X ，Zheng T ，Qiu J ，Hua K ... -  《Journal of Ovarian Research》

Overexpression of long noncoding RNA HOXB-AS3 indicates an unfavorable prognosis and promotes tumorigenesis in epithelial ovarian cancer via Wnt/β-catenin signaling pathway.

Long noncoding RNA HOXB cluster antisense RNA 3 (HOXB-AS3) has been reported to be dysregulated in several tumors. The present study mainly aims at the investigation in how HOXB-AS3 works in epithelial ovarian cancer (EOC) and to elucidate the mechanism involved. Initially, 'GEPIA' was mined to examine the differential expression levels and prognostic value of HOXB-AS3 in EOC patients. The expression of HOXB-AS3 in EOC cell lines and patient specimens was examined with quantitative RT-PCR. Simultaneously, the correlation of HOXB-AS3 expression with a variety of clinicopathological factors and patient survival was analyzed. MTT, colony formation and flow cytometry assays were performed to analyze the cell viability of EOC cells. Wound healing and Transwell assays were carried out to determine EOC cells' capability of migrating and invading. The impact of HOXB-AS3 on EMT and Wnt/β-catenin signaling was explored with the approach of Western blot. We found that in both EOC cell lines and tissues, HOXB-AS3 expression was significantly up-regulated, and its high expression was an independent prognostic marker of poor outcome for EOC patients. In vitro loss-of-function assays revealed that HOXB-AS3 knockdown inhibited EOC cells proliferation, migration, invasion and EMT, and induced EOC cells' apoptosis. Furthermore, we validated that down-regulated HOXB-AS3 attenuated the activity of Wnt/β-catenin signaling to suppress the invasion, migration and proliferation of EOC cells. To sum up, the present study came up with the conclusion that HOXB-AS3 acts as an oncogenic gene in EOC progression through HOXB-AS3-Wnt/β-catenin signaling regulation, providing a novel insight into EOC tumorigenesis.

Zhuang XH ，Liu Y ，Li JL 《-》