Long non-coding RNA CCAT1 promotes metastasis and poor prognosis in epithelial ovarian cancer.

In this study, we reported that long non-coding RNA (lncRNA) CCAT1 was upregulated in epithelial ovarian cancer (EOC) tissues, and was associated with FIGO stage, histological grade, lymph node metastasis and poor survival of EOC patients. Multivariate Cox regression analysis showed that CCAT1 was an independent prognostic indicator. While CCAT1 downregulation inhibited EOC cell epithelial-mesenchymal transition (EMT), migration and invasion, CCAT1 upregulation promoted EOC cell EMT, migration and invasion. We further identified and confirmed that miR-152 and miR-130b were the targets of CCAT1, and CCAT1 functioned by targeting miR-152 and miR-130b. Subsequently, ADAM17 and WNT1, and STAT3 and ZEB1 were confirmed to be the targets of miR-152 and miR-130b, respectively, and could be regulated by CCAT1 in EOC cells. Knockdown of anyone of these four proteins inhibited EOC cell EMT, migration and invasion. Taken together, our study first revealed a critical role of CCAT1-miR-152/miR-130b-ADAM17/WNT1/STAT3/ZEB1 regulatory network in EOC cell metastasis. These findings provide great insights into EOC initiation and progression, and novel potential therapeutic targets and biomarkers for diagnosis and prognosis for EOC.

Cao Y ，Shi H ，Ren F ，Jia Y ，Zhang R ... -  《-》

LncRNA HOXD-AS1 promotes epithelial ovarian cancer cells proliferation and invasion by targeting miR-133a-3p and activating Wnt/β-catenin signaling pathway.

Long non-coding RNA (lncRNA) HOXD cluster antisense RNA 1 (HOXD-AS1) functions as a crucial regulator in the progression and development of tumors. The aim of this study is to unravel the underlying mechanisms of HOXD-AS1 on epithelial ovarian cancer (EOC). 43 paired EOC tissues and adjacent non-tumor tissues were collected postoperatively from patients. QRT-PCR was used to explore HOXD-AS1 expression in both EOC tissues and cell lines. Cell proliferation and invasion were monitored by MTT assay and transwell invasion assay. In the current study, we found that the expression of HOXD-AS1 was upregulated in EOC tissues and cell lines. High HOXD-AS1 expression was correlated with advanced FIGO stage, lymph node metastasis, and poor overall survival in EOC patients. We also showed that HOXD-AS1 promoted cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) via activating Wnt/β-catenin signaling in EOC cells. Furthermore, we found that miR-133a-3p was a direct downstream target of HOXD-AS1 in EOC. HOXD-AS1 promoted cell proliferation, invasion, and EMT process through sponging miR-133a-3p in EOC cells. Our study indicated that lncRNA HOXD-AS1 promoted the proliferation, invasion, and EMT process of EOC cells via targeting miR-133a-3p and activating Wnt/β-catenin signaling pathway.

Zhang Y ，Dun Y ，Zhou S ，Huang XH ... -  《-》

MicroRNA-130b functions as a tumor suppressor by regulating RUNX3 in epithelial ovarian cancer.

To evaluate the clinical significance of microRNA (miR)-130b-Runt domain transcription factor (RUNX3) axis and its effects on oncogenic phenotypes of human epithelial ovarian cancer (EOC). QRT-PCR was performed to detect the expression of miR-130b and RUNX3 mRNA in 100 EOC and 20 normal ovarian tissues. The associations between miR-130b and/or RUNX3 expression and various clinicopathological features of EOC patients were statistically analyzed. Then, the effects of miR-130b-RUNX3 axis on migration and invasion of EOC cells were assessed in vitro. miR-130b expression was downregulated, while RUNX3 mRNA was upregulated, in EOC tissues compared to normal ovarian tissues (both P=0.001). Importantly, the expression level of miR-130b in EOC tissues was negatively correlated with that of RUNX3 mRNA significantly. Additionally, miR-130b-low and/or RUNX3-high expression were all closely correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage (all P<0.05). Moreover, overexpression of miR-130b reduced the expression of RUNX3 and inhibited cancer cell migration and invasion of EOC cells, whereas knockdown of miR-130b increased the expression of RUNX3 and promoted cancer cell migration and invasion of EOC cells. After that, the impaired motility of the miR-130b overexpression cells was recovered partly by the expression of RUNX3. Furthermore, the knockdown of RUNX3 also gave rise to a decrease in cell migration and invasion. Our data reveal that the dysregulation of miR-130b-RUNX3 axis may play important roles in EOC development and progression, and the loss of miR-130b may contribute to the malignant biological behavior of EOC cells via regulating the expression of RUNX3, implying their potentials as promising markers for predicting EOC progression and as candidate targets for gene therapy.

Paudel D ，Zhou W ，Ouyang Y ，Dong S ，Huang Q ，Giri R ，Wang J ，Tong X ... -  《-》

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 ... -  《-》

MicroRNA-150 predicts a favorable prognosis in patients with epithelial ovarian cancer, and inhibits cell invasion and metastasis by suppressing transcriptional repressor ZEB1.

Jin M ，Yang Z ，Ye W ，Xu H ，Hua X ... -  《PLoS One》