LncRNA NEAT1 contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEB1 expression via miR-194

Abstract

BackgroundChemoresistance is one of the major obstacles for cancer therapy in the clinic. Nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported as an oncogene in most malignancies such as lung cancer, esophageal cancer, and gastric cancer. This study is designed to investigate the function of NEAT1 in paclitaxel (PTX) resistance of ovarian cancer and its potential molecular mechanism.Patients and methodsThe expressions of NEAT1 and miR-194 in ovarian cancer tissues and cells were estimated by quantitative real-time polymerase chain reaction (qRT-PCR). MTT, flow cytometry, and Western blot assays were used to assess the effect of NEAT1 on PTX resistance in PTX-resistant ovarian cancer cells. Luciferase reporter assay was applied to examine the association between NEAT1, zinc finger E-box-binding homeobox 1 (ZEB1) and miR-194. Xenograft tumor model was established to confirm the biological role of NEAT1 in PTX resistance of ovarian cancer in vivo.ResultsNEAT1 was upregulated, and miR-194 was downregulated in PTX-resistant ovarian cancer tissues and cells. Functionally, NEAT1 knockdown enhanced cell sensitivity to PTX via promoting PTX-induced apoptosis in vitro. NEAT1 was identified as a molecular sponge of miR-194 to upregulate ZEB1 expression. Mechanistically, NEAT1-knockdown-induced PTX sensitivity was mediated by miR-194/ZEB1 axis. Moreover, NEAT1 knockdown improved PTX sensitivity of ovarian cancer in vivo.ConclusionNEAT1 contributed to PTX resistance of ovarian cancer cells at least partly through upregulating ZEB1 expression by sponging miR-194, elucidating a novel regulatory pathway of chemoresistance in PTX-resistant ovarian cancer cells and providing a possible long noncoding RNA (lncRNA)-targeted therapy for ovarian cancer.

Long non‐coding RNA NEAT1 promoted ovarian cancer cells’ metastasis through regulation of miR‐382‐3p/ROCK1 axial

“…10 A member of the lncRNA, nuclear enriched abundant transcript 1 (NEAT1) is reported as an oncogene in various malignant tumors, including hepatocellular carcinoma, non-small cell lung cancer, nasopharyngeal carcinoma, breast cancer and OC. [11][12][13][14][15][16] report that NEAT1 contributed Yangcheng Liu and Yong Wang contributed equally to this work. to paclitaxel (PTX) resistance of OC cells through upregulating ZEB1 expression by sponging of .…”

“…A member of the lncRNA, nuclear enriched abundant transcript 1 (NEAT1) is reported as an oncogene in various malignant tumors, including hepatocellular carcinoma, non‐small cell lung cancer, nasopharyngeal carcinoma, breast cancer and OC . An (2017) report that NEAT1 contributed to paclitaxel (PTX) resistance of OC cells through upregulating ZEB1 expression by sponging of microRNA‐194 (miR‐194) . Ding (2017) report that NEAT1 promoted OC cells’ proliferation and apoptosis through regulation of microRNA‐34a‐5p (miR‐34a‐5p)/B‐cell lymphoma‐2 (BCL2) .…”

ZEB1 Promotes Chemoresistance to Cisplatin in Ovarian Cancer Cells by Suppressing SLC3A2

“…Downregulation of ZEB1 has been found to inhibit EMT of ovarian cancer cells [12]. ZEB1 also acts as the target of miRs, mediating the inhibitory effect on EMT of ovarian cancer cells [8, 10, 14]. Dysregulation of ZEB1 is also involved in emodin-induced inhibition of EMT in epithelial ovarian cancer cells [13].…”

“…ZEB1 functions as an inducer of tumor invasion, metastasis, and resistance to chemo- and radiotherapy, in large part by mediating the epithelial to mesenchymal transition (EMT) in cancer cells [7]. In ovarian cancer, it has been found that ZEB1 expression increases and ZEB1 upregulation mediates the chemoresistance induced by several long noncoding RNAs and microRNAs (miRs) [8-11]. It is also reported that downregulation of ZEB1 inhibits EMT of ovarian cancer cells [12].…”

Overexpression of the lncRNA FER1L4 inhibits paclitaxel tolerance of ovarian cancer cells via the regulation of the MAPK signaling pathway

“…Drug resistance has been a major reason for the failure of chemotherapy. Particularly, resistance to paclitaxel (PTX) has been one of the primary causes of chemotherapy resistance in clinical therapeutic applications of ovarian carcinoma for a long time . PTX is a natural medication used as the first‐line chemotherapeutic agent for the treatment of OC because it does not induce cross‐resistance with platinum‐based drugs .…”