LncRNA TP73-AS1 is a novel regulator in cervical cancer via miR-329-3p/ARF1 axis

Cervical cancer holds one of the highest morbidity and mortality in various types of cancers. It even leads to the most number of cancer-related deaths of women. A lot of research has indicated that the anomalous expression of long noncoding RNAs (lncRNAs) would induce carcinogenesis and is associated with poor prognosis of patients with cancer. However, the function and mechanism of many lncRNAs still call for further research. Tumor Protein P73 Antisense RNA 1 (TP73-AS1) is no exception. LncRNA TP73-AS1 has been found to promote cancer progressions in various cancers. It is upregulated in cervical cancer cells. The proliferation and migration ability of cervical cancer cells can also be boosted by TP73-AS1 in return. Meanwhile, miRNA-329-3p is downregulated in cervical cancer cells and could bind with both TP73-AS1 and ADP Ribosylation Factor 1 (ARF1). TP73-AS1 inhibited miR-329-3p expression while miR-329-3p inhibited ARF1 expression. More importantly, TP73-AS1 can positively regulate ARF1 expression. Based on all these experiments, TP73-AS1 regulates ARF1 expression by competitively binding with miR-329-3p, thus regulating cervical cancer progression. Further rescue assays confirmed TP73-AS1 regulates cervical cell proliferation and migration via miR-329-3p/ARF1. TP73-AS1 might serve as a novel regulator in cervical cancer.     

LncRNA TP73-AS1 predicts poor prognosis and functions as oncogenic lncRNA in osteosarcoma

TP73 antisense RNA 1 (TP73-AS1), a novel long noncoding RNA (lncRNA), has been suggested to be deregulated in various human cancers and serve as a tumor suppressor or promoter, depending on tumor types. The role of TP73-AS1 in osteosarcoma is still unknown. In our results, TP73-AS1 was highly expressed in osteosarcoma tissue samples and cell lines compared with matching adjacent nontumor tissue specimens and a normal human osteoblast cell line, respectively. Moreover, high expression of TP73-AS1 was statistically associated with advanced Enneking stage, large tumor size, present distant metastasis, and poor histological grade, while exhibiting no statistical association with age, sex, and tumor site. The survival analyses showed that patients with osteosarcoma with high expression of TP73-AS1 obviously had lower overall survival than osteosarcoma patients with low expression of TP73-AS1, and high expression of TP73-AS1 was an independent poor prognostic factor for osteosarcoma patients. The experiments in vitro indicated that inhibition of TP73-AS1 expression depressed osteosarcoma cell viability, migration, and invasion, and arrested cell cycle. In conclusion, TP73-AS1 serves as oncogenic lncRNA participated in osteosarcoma progression.     

LncRNA TP73-AS1/miR-539/MMP-8 axis modulates M2 macrophage polarization in hepatocellular carcinoma via TGF-β1 signaling

PurposeOur study aimed to study the role of lncRNA TP73-AS1/miR-539/MMP-8 axis in modulating M2 macrophage polarization in hepatocellular carcinoma (HCC).MethodsThe gene expression levels of TP73-AS1, miR-539 and MMP-8 were modified by transfection with the overexpression or knockdown vectors. The patient survival rate was analyzed using Kaplan-Meier method. The levels of TP73-AS1, miR-539, MMP-8 and M1/2 macrophage polarization markers were analyzed by qRT-PCR, western blot, and flow cytometry. The release of TGF-β1 in the supernatant was determined by ELISA assay. The interaction between TP73-AS1, miR-539 and MMP-8 was analyzed by bioinformatics analysis and dual-luciferase reporter assays. Mouse xenograft model was further established to examine the therapeutic effects of the TP73-AS1 knockdown and miR-539 overexpression in vivo.ResultsWe found TP73-AS1 and MMP-8 upregulation, and miR-539 downregulation in HCC tissues and cell lines. Lower TP73-AS1 and MMP-8 expressions and higher miR-539 expression were associated with higher survival rate of patients. M2-macrophage markers CD206, Arg-1 and CD163 were significantly upregulated in the tumor tissues. TP73-AS1 negatively and directly regulated miR-539 and knockdown of TP73-AS1 inhibited MMP-8 expression and M2 macrophage polarization. Also, overexpression of miR-539 suppressed M2 macrophage polarization by negatively regulating MMP-8. Furthermore, knockdown of MMP-8 also restrained M2 macrophage polarization via inhibiting TGF-β1 signaling. We also found knockdown of TP73-AS1 or overexpression of miR-539 inhibited HCC tumor growth and M2 macrophage infiltration in vivo.ConclusionOur study demonstrated lncRNA TP73-AS1 negatively regulated miR-539 to promote MMP-8 expression, which activated TGF-β1 signaling to induce M2 macrophage polarization in HCC.     

Long noncoding RNA FEZF1-AS1 predicts poor prognosis and modulates pancreatic cancer cell proliferation and invasion through miR-142/HIF-1α and miR-133a/EGFR upon hypoxia/normoxia

Nowadays, pancreatic cancer (PC) remains the most lethal tumor, partially due to the invasive and treatment-resistant phenotype induced by the extent of hypoxic stress within the tumor tissue. According to previous studies, miR-142/HIF-1α and miR-133a/EGFR could modulate PC cell proliferation under hypoxic and normoxic conditions, respectively. In the present study, FEZF1-AS1, a recently described oncogenic long noncoding RNA, was predicted to target both miR-142 and miR-133a; thus, we hypothesized that FEZF1-AS1 might affect PC cell proliferation through these two axes under hypoxic or normoxic conditions. In PC cell lines, FEZF1-AS1 acted as an oncogene via promoting PC cell proliferation and invasion through miR-142/HIF-1α axis under hypoxic condition; however, FEZF1-AS1 failed to affect the protein levels of HIF-1α and VEGF under the normoxic condition, suggesting the existence of another signaling pathway under normoxic condition. As predicted by an online tool, FEZF1-AS1 could target miR-133a to inhibit its expression; under the normoxic condition, FEZF1-AS1 exerted its effect on PC cell lines through miR-133a/EGFR axis. Taken together, FEZF1-AS1 might be a promising target in controlling the aberrant proliferation and invasion of PC cell lines.     

AGAP2-AS1 serves as an oncogenic lncRNA and prognostic biomarker in glioblastoma multiforme

Long noncoding RNA (lncRNA) AGAP2 antisense RNA 1 (AGAP2-AS1) has been suggested to function as an oncogenic lncRNA in lung cancer, breast cancer, and anaplastic glioma. However, the expression pattern and molecular mechanism of AGAP2-AS1 in glioblastoma multiforme (GBM) remains unknown. The purpose of this study is to present more evidence about the clinical and biological function of AGAP2-AS1 in GBM. In our results, we found AGAP2-AS1 expression was increased in GBM compared with adjacent normal brain tissues or low-grade glioma tissues, and there was no significantly different between low-grade glioma tissues and normal tissues. Kaplan-Meier survival analysis indicated patients with GBM having high-expression of AGAP2-AS1 had shorter overall survival time than those with low expression of AGAP2-AS1. The loss-of-function studies showed that downregulation of AGAP2-AS1 depressed cell proliferation, migration, and invasion, and promoted cell apoptosis in GBM. In summary, AGAP2-AS1 is a prognostic biomarker for patients with GBM, and functions as an oncogenic lncRNA to modulate GBM cell proliferation, apoptosis, migration, and invasion, which suggests that AGAP2-AS1 is potential therapeutic target for GBM.     

LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer

LncRNAs play essential regulatory roles in pancreatic cancer (PC) tumorigenesis and progression. We aimed to investigate the role of lncRNA CERS6-AS1 in PC. CERS6-AS1 expression was determined in PC tissues and cell lines by PCR analysis. The roles of CERS6-AS1 on proliferation, migration, invasion, and epithelial to mesenchymal transition (EMT) were confirmed via CCK-8 assay, EDU assay, transwell assay, wound healing assay, and western blot assay. Besides, the interaction between CERS6-AS1 and their target genes was verified by luciferase report assays and RIP assays. Animal assays and clinical data analysis were performed to validate the functions in vivo. We found that lncRNA CERS6-AS1 was highly expressed in PC tissues and cells. Additionally, high expression of CERS6-AS1 was obviously associated with poor prognosis. Functional assays demonstrated that CERS6-AS1 downregulation significantly inhibited PC cell growth and migration. Moreover, CERS6-AS1 exerted as a molecular sponge for miR-217-5p (miR-217), and miR-217 was confirmed as a potential target of CERS6-AS1. Subsequently, miR-217 suppressed PC cell proliferation and metastasis by directly targeting YWHAG, which interacted with RAF1 and promoted its phosphorylation, leading to RAF1-mediated ERK signaling activation and translocation of phosphorylated ERK from the cytoplasm to the nucleus. Mechanically, CERS6-AS1 silencing significantly inhibited PC cell proliferation and metastasis via a miR-217/YWHAG/RAF1 signaling axis. CERS6-AS1 exerts as a carcinogen in PC to promote malignant features and behaves as a competitive endogenous RNA for miR-217. We identified CERS6-AS1 as a potential biomarker or therapeutic target to improve PC diagnosis and treatment outcomes.Subject terms: Oncogenes, Tumour biomarkers     

LncRNA MNX1-AS1 promotes the progression of cervical cancer through activating MAPK pathway

Long noncoding RNAs (lncRNAs) have been discovered as significant regulators in a wide range of human cancers. Among them, lncRNA MNX1-AS1 has been proved to be an oncogene in ovarian cancer and glioblastoma. However, the regulatory mechanism of MNX1-AS1 in cervical cancer remains to be understood. Therefore, this study planned to explore the role of MNX1-AS1 in cervical cancer. In the beginning, we found that the expression of MNX1-AS1 was obviously upregulated in cervical cancer tissues and cell lines. Kaplan-Meier survival analysis revealed that patients with higher MNX1-AS1 expression level suffered from shorter overall survival time than those with lower MNX1-AS1 level. Moreover, by loss-of-function and gain-of-function assay, the effect of MNX1-AS1 on cell proliferation and apoptosis was examined on cellular level. Results showed that the proliferation of Hela cells was significantly inhibited and apoptosis enhanced by the transfection of shMNX1-AS1, while overexpressing MNX1-AS1 in E6E7 cells presented the contrary results. As for mechanism investigation, it was demonstrated that overexpression of MNX1-AS1 significantly improved the expression of p-ERK1/2 and p-JNK. And the effects of MNX1-AS1 on cell proliferation and apoptosis would be diminished after inactivating the phosphorylation of either ERK or JNK. Taken together, it was identified that MNX1-AS1 promoted proliferation and inhibited apoptosis of cervical cancer cells through MAPK pathway.     

lncRNA FLVCR1-AS1 silencing inhibits lung cancer cell proliferation,migration, and invasion by inhibiting the activity of the Wnt/β-catenin signaling pathway

Long noncoding RNAs have been reported to be essential regulators in several human diseases, including tumorigenesis. A recent report revealed that FLVCR1-AS1 promotes the progression of hepatocellular carcinoma. However, whether FLVCR1-AS1 is involved in lung cancer remains unclear. In this study, we found that the expression of FLVCR1-AS1 was increased in lung cancer tissues according to The Cancer Genome Atlas database. Similarly, FLVCR1-AS1 was significantly upregulated in lung cancer cell lines. Knockdown of FLVCR1-AS1 dramatically reduced the cell proliferation, migration, and invasion of SPCA1 and A549. Mechanistically, we found that the expression levels of CTNNB1, SOX4, CCND1, CCND2, c-MYC, as well as nucleus β-catenin were decreased in lung cancer cells after FLVCR1-AS1 silencing. Thus, FLVCR1-AS1 positively regulates the activation of the Wnt/β-catenin pathway. Overexpression of CTNNB1 reversed the effect of FLVCR1-AS1 knockdown on A549 cells. In sum, FLVCR1-AS1 silencing inhibited the proliferation, migration, and invasion of lung cancer cells by inhibiting the activity of the Wnt/β-catenin signaling pathway.     

Cucurbitacin B suppresses proliferation of pancreatic cancer cells by ceRNA: Effect of miR-146b-5p and lncRNA-AFAP1-AS1

Cucurbitacin B (CuB) is a natural tetracyclic triterpene product that displays antitumor activity against a wide variety of cancers. In this study, we explored the antipancreatic cancer activity of CuB via the inhibition of expression of the cancer-related long noncoding RNA, actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1). CuB arrested pancreatic cancer (PC) cells in the G2/M cell cycle phase by suppressing the expression of AFAP1-AS1. Insights into the mechanisms of competing endogenous RNAs (ceRNAs) gained from bioinformatics analysis and luciferase activity assays showed that the epidermal growth factor receptor (EGFR) and AFAP1-AS1 directly compete for miR-146b-5p binding. CuB-induced high miR-146b-5p expression and inhibited the expression of AFAP1-AS1. In summary, reducing the expression of endogenous AFAP1-AS1 effectively increased the available concentration of miR-146b-5p in PC, whereas miR-146b-5p overexpression prevented the expression of endogenous AFAP1-AS1. In particular, we hypothesized that AFAP1-AS1 might act as a ceRNA, effectively becoming a sponge for miR-146b-5p, thereby activating the expression of the EGFR. Thus, CuB suppresses the proliferation, in vitro and in vivo, of PC cells through the ceRNA effect of AFAP1-AS1 on miR-146b-5p.     

Long noncoding RNA SOX21-AS1 promotes cervical cancer progression by competitively sponging miR-7/VDAC1

Growing evidence has shown that long noncoding RNAs (lncRNAs) play crucial roles in cervical cancer. Dy000sregulation of lncRNA SOX21 antisense RNA 1 (SOX21-AS1) has been reported in several tumors. However, its expression pattern and potential biological function in cervical cancer (CC) have not been investigated. In this study, we first reported that SOX21-AS1 expression was significantly upregulated in both CC tissues and cell lines. High expression of SOX21-AS1 was found to be significantly correlated with Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis and depth of cervical invasion. Further clinical assay confirmed that high SOX21-AS1 expression was associated with shorter overall survival and could be used as a potential prognostic biomarker for CC patients. Functional investigation showed that knockdown of SOX21-AS1 suppressed CC cells proliferation, migration, and invasion, as well as epithelial to mesenchymal transition progress. Furthermore, our data showed that microRNA-7 (miR-7) interacted with SOX21-AS1 by directly targeting the miRNA-binding site in the SOX21-AS1 sequence, and quantitative real-time polymerase chain reaction results showed overexpression of SOX21-AS1 decreased the levels of miR-7 in CC cells. Moreover, we confirmed that miR-7 directly targeted the 3′-untranslated region of voltage dependent anion channel 1 (VDAC1). Final in vitro assay suggested that in CC cells with SOX21-AS1, VDAC1 overexpression resulted in an increase of cell proliferation, migration, and invasion. Overall, our findings illuminate how SOX21-AS1 formed a regulatory network to confer an oncogenic function in CC and SOX21-AS1 could be regarded as an efficient therapeutic target and potential biomarker for CC patients.     

IncRNA MAPKAPK5-AS1 promotes proliferation and migration of thyroid cancer cell lines by targeting miR-519e-5p/YWHAH

Thyroid cancer is a common malignant tumour of the endocrine system and ranks ninth in cancer incidence worldwide. An extensive body of evidence has demonstrated that lncRNAs play a critical role in the progression of thyroid cancer. The lncRNA MAPKAPK5-AS1 has been reported to be abnormally expressed and to play a role in the development of various human cancers. However, MAPKAPK5-AS1’s potential role in thyroid cancer progression remains unknown. The objective of our study was to explore the role and mechanism of MAPKAPK5-AS1 in thyroid cancer cells and provide a potential target for its biological diagnosis and treatment. We transfected sh-MAPKAPK5-AS1 and sh-NC into BCPAP and TPC-1 cells for loss-of-function assays. Results of RT-qPCR analysis demonstrated that MAPKAPK5-AS1 was more highly expressed in thyroid cancer cells compared to normal cells. Functional assays demonstrated that interfering with the expression of MAPKAPK5-AS1 notably repressed proliferation and invasion and accelerated apoptosis of BCPAP and TPC-1 cells. Mechanistically, we found that miR-519e-5p was negatively regulated by MAPKAPK5-AS1 and that tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) was a target of miR-519e-5p. Additionally, rescue assays demonstrated that downregulation of MAPKAPK5-AS1 expression inhibited cell proliferation, migration, and invasion and promoted apoptosis by sponging miR-519e-5p, thereby increasing YWHAH expression. Ultimately, our study revealed that MAPKAPK5-AS1 promotes proliferation and migration of thyroid cancer cells by targeting the miR-519e-5p/YWHAH axis, which provides novel insight into the development and progression of thyroid cancer.Key words: IncRNA MAPKAPK5-AS1, MiR-519e-5p, YWHAH, thyroid cancer cell     

Long noncoding RNA MNX1-AS1 contributes to lung cancer progression through the miR-527/BRF2 pathway

Lung cancer belongs to a leading popular and malignant cancer around the world. However, the root mechanism underlying lung cancer progression remains unclear. Recently, long noncoding RNA (lncRNA) has been identified as important for tumorigenesis. LncRNA MNX1-AS1 is proven to regulate colon adenocarcinoma, cervical cancer, glioblastoma, and ovarian cancer. Whether MNX1-AS1 participates in lung cancer needs investigation. In our research, we found that MNX1-AS1 was dramatically upregulated in lung cancer. MNX1-AS1 upregulation indicated poor prognosis in lung cancer patients. Functionally, MNX1-AS1 promoted lung cancer progression through regulating proliferation, migration, and invasion. Mechanistically, MNX1-AS1 was found to locate in the cytoplasm and interact with miR-527. Through inhibiting miR-527 availability, MNX1-AS1 facilitated BRF2 expression. Restoration of BRF2 rescued defects of proliferation, migration, and invasion caused by MNX1-AS1 knockdown. Taken together, our study found a novel signaling pathway, namely MNX1-AS1/miR-527/BRF2 axis, involved in lung cancer progression.     

TP73‐AS1 promotes breast cancer cell proliferation through miR‐200a‐mediated TFAM inhibition

P73 antisense RNA 1T (TP73‐AS1 or PDAM) is a long non‐coding RNA, which can regulate apoptosis through regulation of p53 signaling‐related anti‐apoptotic genes. An abnormal change of TP73‐AS1 expression was noticed in cancers. The effects of TP73‐AS1 in breast cancer (BC) growth and the underlying mechanism remain unclear so far. In the present study, the effect of TP73‐AS1 in BC cell lines and clinical tumor samples was detected so as to reveal its role and function. In the present study, TP73‐AS1 was specifically upregulated in BC tissues and BC cell lines and was correlated to a poorer prognosis in patients with BC. TP73‐AS1 knocking down suppressed human BC cell proliferation in vitro through regulation of TFAM. In our previous study, we demonstrated that miR‐200a inhibits BC cell proliferation through targeting TFAM; here we revealed that TP73‐AS1 could regulate miR‐200a through direct targeting. Moreover, TP73‐AS1 might compete with TFAM for miR‐200a binding thus to promote TFAM expression. Data from the present study revealed that TP73‐AS1 promoted BC cell proliferation through acting as a competing endogenous RNA (ceRNA) by sponging miR‐200a. In conclusion, we regarded TP73‐AS1 as an oncogenic lncRNA promoting BC cell proliferation and a potential target for human BC treatment.     

Long noncoding RNA FLVCR1-AS1 aggravates biological behaviors of glioma cells via targeting miR-4731-5p/E2F2 axis

Long noncoding RNAs (lncRNAs) display essential roles in cancer progression. FLVCR1-AS1 is a rarely investigated lncRNAs involved in various human cancers, such as hepatocellular carcinoma and lung cancer. However, its function in glioma has not been clarified. In our study, we found that FLVCR1-AS1 was highly expressed in glioma tissues and cell lines. And upregulation of FLVCR1-AS1 predicted poor prognosis in patients with glioma. Moreover, FLVCR1-AS1 knockdown inhibited proliferation, migration and invasion of glioma cells. Through bioinformatics analysis, we identified that FLVCR1-AS1 was a sponge for miR-4731-5p to upregulate E2F2 expression. Moreover, rescue assays indicated that FLVCR1-AS1 modulated E2F2 expression to participate in glioma progression. Altogether, our research demonstrates that the FLVCR1-AS1/miR-4731-5p/E2F2 axis is a novel signaling in glioma and may be a potential target for tumor therapy.     

Inhibition of DCLK1 kinase reverses epithelial-mesenchymal transition and restores T-cell activity in pancreatic ductal adenocarcinoma

Immunotherapy has recently become a promising cancer therapy with extensive applications of immune checkpoint inhibitors (ICIs). However, pancreatic ductal adenocarcinoma (PDAC) appears to be unresponsive to immunotherapy due to the immunosuppressive microenvironment. Recent studies showed that cancer stem cell marker DCLK1 promoted the initiation and development of PDAC. Nevertheless, the mechanism driving this process remains unclear. Here, by performing gain-of-function investigations in PDAC cell lines, we demonstrate that both DCLK1 long (DCLK1-iso1, DCLK1-AS) and short (DCLK1-iso4, DCLK1-BL) isoforms can efficiently activate EMT leading to tumor migration and invasion. Consistent with experiments in vitro, bioinformatic analysis demonstrates that DCLK1 may act as a driver of EMT activation in PDAC. Further analysis showed that EMT was associated with an immunosuppressive microenvironment, which includes more immunosuppressive cells and chemokines, and patients with a higher EMT score were less sensitive to immune checkpoint inhibitors according to the TIDE (Tumor Immune Dysfunction and Exclusion) algorithm. Multiplexed immunofluorescence results demonstrated the close correlation between DCLK1, EMT and immunosuppression in PDAC patients. The findings were further confirmed in vivo reflected by decreased CD4+, CD8+ T cells and increased M2 macrophages as well as E-cad loss in DCLK1-overexpressing subcutaneous tumors. Importantly, the highly-specific DCLK1 inhibitor (DCLK1-IN-1) was able to effectively block EMT process and restore T-cell activity. Altogether, our data demonstrate that DCLK1 is strongly associated with tumor immune escape in PDAC and inhibiting DCLK1 kinase activity may be a promising therapeutic modality.     

miR-186 and 326 Predict the Prognosis of Pancreatic Ductal Adenocarcinoma and Affect the Proliferation and Migration of Cancer Cells

MicroRNAs can function as key tumor suppressors or oncogenes and act as biomarkers for cancer diagnosis or prognosis. Although high-throughput assays have revealed many miRNA biomarkers for pancreatic ductal adenocarcinoma (PDAC), only a few have been validated in independent populations or investigated for functional significance in PDAC pathogenesis. In this study, we correlated the expression of 36 potentially prognostic miRNAs within PDAC tissue with clinico-pathological features and survival in 151 Chinese patients. We then analyzed the functional roles and target genes of two miRNAs in PDAC development. We found that high expression of miR-186 and miR-326 predict poor and improved survival, respectively. miR-186 was over-expressed in PDAC patients compared with controls, especially in patients with large tumors (>2 cm), lymph node metastasis, or short-term survival (< 24 months). In contrast, miR-326 was down-regulated in patients compared with controls and displayed relatively increased expression in the patients with long-term survival or without venous invasion. Functional experiments revealed that PDAC cell proliferation and migration was decreased following inhibition and enhanced following over-expression of miR-186. In contrast, it was enhanced following inhibition and decreased after over-expression of miR-326. A luciferase assay indicated that miR-186 can bind directly to the 3′-UTR of NR5A2 to repress gene expression. These findings suggest that miR-186 over-expression contributes to the invasive potential of PDAC, likely via suppression of NR5A2, thereby leading to a poor prognosis; high miR-326 expression prolongs survival likely via the decreasing invasive potential of PDAC cells. These two miRNAs can be used as markers for clinical diagnosis and prognosis, and they represent therapeutic targets for PDAC.     

The decreased lncRNA ZEB2-AS1 in pre-eclampsia controls the trophoblastic cell line HTR-8/SVneo's invasive and migratory abilities via the miR-149/PGF axis

Pre-eclampsia (PE) is a pregnancy disease that causes maternal death and threatens the health of newborns. Accumulating evidence has revealed the essential roles of long noncoding RNAs (lncRNAs) in the progression of PE. The present investigation determined lncRNA ZEB2 antisense RNA 1 (ZEB2-AS1) expression in PE and looked into the potential role of ZEB2-AS1 in modulating trophoblastic cell functions. Quantitative real-time polymerase chain reaction evaluated gene expression. Western blot analyzed the placental growth factor (PGF) protein level. Cell counting kit-8 and Transwell invasion assays assessed the proliferative and invasive abilities of placental trophoblast cells, respectively. Wound healing assay determined cell migratory potentials. Dual-luciferase reporter assay assessed the targeting relationship among ZEB2-AS1, miR-149, and PGF. Downregulation of lncRNA ZEB2-AS1 was detected in placentas from patients with PE when compared with those from normal pregnancies. Moreover, ZEB2-AS1 upregulation markedly promoted proliferative, migratory, and invasive potentials in HTR-8/SVneo cells, while knockdown of ZEB2-AS1 had the opposite effects. The effects on HTR-8/SVneo cells mediated by ZEB2-AS1 was correlated with the miR-149/PGF axis. These findings indicate that ZEB2-AS1 contributes to PE progression by affecting cell proliferative and invasive capacities via the miR-149/PGF axis in HTR-8/SVneo cells. In sum, we identified that ZEB2-AS1 was a novel aberrantly expressed lncRNA in the placentas of PE patients and lncRNA ZEB2-AS1 modulated trophoblastic cell line HTR-8/SVneo's proliferative and invasive potentials via targeting the miR-149/PGF axis.