RNA methylation-mediated LINC01559 suppresses colorectal cancer progression by regulating the miR-106b-5p/PTEN axis

Long noncoding RNAs (lncRNAs) regulate multiple biological effects in cancers. Recently, RNA methylation has been found to modify not only coding RNAs but also some noncoding RNAs. How RNA methylation affects lncRNAs to affect colorectal cancer (CRC) progression remains elusive. The expression of LINC01559 was explored through RNA sequencing, quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). The preliminary exploration of its function was performed using Western blotting (WB) and immunohistochemistry (IHC). Functional experiments in vitro and in vivo were conducted to explore the biological functions of LINC01559 in CRC. The LINC01559/miR-106-5p/PTEN axis was verified through fluorescence in situ hybridization (FISH), luciferase assays, and rescue experiments. RIP-sequencing, m6A RNA immunoprecipitation (MeRIP) assays and bioinformatic analysis were conducted to determine the upstream mechanism of LINC01559. The results showed that LINC01559 was downregulated in CRC compared with normal controls. Lower expression of LINC01559 in CRC patients predicted a poor prognosis. In addition, PTEN was found to be positively correlated with LINC01559, and miR-106b-5p could be the link between LINC01559 and PTEN. Then, silencing LINC01559 restored the malignant phenotype of CRC cells, while cotransfection of miR-106b-5p inhibitor neutralized this effect. Mechanistically, we found abundant m6A modification sites on LINC01559. Then, we uncovered these sites as potential targets of METTL3 through experiments in vivo. The results revealed a negative functional regulation of the LINC01559/miR-106b-5p/PTEN axis in CRC progression and explored a new mechanism of METTL3-mediated m6A modification on LINC01559. These results elucidate a novel potential therapeutic target for CRC treatment.     

MicroRNA-26b-5p enhances T cell responses by targeting PIM-2 in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is a common tumor malignancy threatening a significant number of people worldwide. Although microRNAs (miRNAs) have been shown to play essential role in tumorigenesis, little is known about their role in T cells functions during HCC progression.MethodsThe abundances of miR-26b-5p were detected in HCC tissues or cells, T cells and H22 cells by quantitative real-time polymerase chain reaction (qRT-PCR). Regulation effect of miR-26b-5p on proviral integrations of moloney virus 2 (PIM2) was investigated by qRT-PCR, western blot (WB) and immunohistochemical analysis. The effect of miR-26b-5p and PIM-2 on cytokines secretion in CD4+ and CD8+ cells was evaluated by commercial enzyme linked immunosorbent assays (ELISA) kit. The interaction between miR-26b-5p and PIM-2 was probed by luciferase activity and RNA immunoprecipitation (RIP). H22 subcutaneous model was established to investigate the interaction of miR-26b-5p with HCC and immune competence.ResultsThe abundance of miR-26b-5p was decreased in HCC and associated with poor survival. Addition of miR-26b-5p contributed to secretion of tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6) and IL-2 in CD4+ and CD8+ cells. Interestingly, PIM-2 was negatively regulated by miR-26b-5p and PIM-2 knockdown reversed anti-miR-26b-5p-mediated immunosuppression. Moreover, inhibitory effect of miR-26b-5p on HCC tumorigenesis was dependent on immune competence.ConclusionsmiR-26b-5p enhanced T cells responses by targeting PIM-2 in HCC, uncovering a promising therapeutic opportunity of HCC through reactivating immune system.     

Bone marrow mesenchymal stem cells-derived exosomal microRNA-19b-1-5p reduces proliferation and raises apoptosis of bladder cancer cells via targeting ABL2

BackgroundExosomes are involved in intercellular communication via specialized molecular cargo, such as microRNAs (miRNAs). However, the mechanisms underlying exosomal miR-19b-1-5p in bladder cancer remain largely unknown, thus, we aim to investigate the effect of exosomal miR-19b-1-5p on bladder cancer with the involvement of non-receptor protein tyrosine kinase Arg (ABL2).MethodsmiR-19b-1-5p and ABL2 expression were tested in bladder cancer. miR-19b-1-5p inhibition/elevation assays were conducted to determine its role in bladder cancer. Exosomes were extracted from bone marrow mesenchymal stem cells (BMSCs). Exosomes and T24 cells were co-cultured to verify their function in biological characteristics of bladder cancer cells.ResultsmiR-19b-1-5p was down-regulated while ABL2 was upregulated in bladder cancer. Exosomal miR-19b-1-5p suppressed malignant behaviors of bladder cancer cells, and also inhibited tumor growth in vivo. Up-regulated ABL2 mitigated the effects of miR-19b-1-5p up-regulation on bladder cancer cells.ConclusionBMSCs-derived exosomal miR-19b-1-5p suppresses bladder cancer growth via decreasing ABL2.     

LINC00152 promotes cell cycle progression in hepatocellular carcinoma via miR-193a/b-3p/CCND1 axis

Long intergenic non-coding RNA 00152 (LINC00152) is aberrantly expressed in various human malignancies and plays an important role in the pathogenesis. Here, we found that LINC00152 is upregulated in hepatocellular carcinoma (HCC) tissues as compared to adjacent non-neoplastic tissues; gain-and-loss-of-function analyses in vitro showed that LINC00152 facilitates HCC cell cycle progression through regulating the expression of CCND1. LINC00152 knockdown inhibits tumorigenesis in vivo. MS2-RIP analysis indicated that LINC00152 binds directly to miR-193a/b-3p, as confirmed by luciferase reporter assays. Furthermore, ectopic expression of LINC00152 partially halted the decrease in CCND1 expression and cell proliferation capacity induced by miR-193a/b-3p overexpression. Thus, LINC00152 acts as a competing endogenous RNA (ceRNA) by sponging miR-193a/b-3p to modulate its target gene, CCND1. Our findings establish a ceRNA mechanism regulating cell proliferation in HCC via the LINC00152/miR-193a/b-3p/CCND1 signalling axis, and identify LINC00152 as a potential therapeutic target for HCC.     

Family of microRNA-146 Regulates RARβ in Papillary Thyroid Carcinoma

Retinoic acid is a promising tool in adjuvant cancer therapies, including refractory thyroid cancer, and its biological role is mediated by the retinoic acid receptor beta (RARβ). However, expression of RARβ is lowered in papillary thyroid carcinoma (PTC), contributing to promotion of tumor growth and inefficiency of retinoic acid and radioactive iodine treatment. The causes of aberrant RARB expression are largely unknown. We hypothesized that the culpable mechanisms include the action of microRNAs from the miR-146 family, previously identified as significantly upregulated in PTC tumors. To test this hypothesis, we assessed the expression of RARB as well as miR-146a-5p and miR-146b-5p in 48 PTC tumor/normal tissue pairs by Taqman assay to reveal that the expression of RARB was 3.28-fold decreased, and miR-146b-5p was 28.9-fold increased in PTC tumors. Direct interaction between miRs and RARB was determined in the luciferase assay and further confirmed in cell lines, where overexpression of miR-146a-5p and miR-146b-5p caused a 31% and 33% decrease in endogenous RARB mRNA levels. Inhibition of miR-146a and miR-146b resulted in 62.5% and 45.4% increase of RARB, respectively, and a concomitant decrease in proliferation rates of thyroid cancer cell lines, analyzed in xCELLigence system.We showed that two microRNAs of the miR-146 family directly regulate RARB. Inhibition of miRs resulted in restoration of RARB expression and decreased rates of proliferation of thyroid cancer cells. By restoring RARB levels, microRNA inhibitors may become part of an adjuvant therapy in thyroid cancer patients.     

Novel splice variants of LINC00963 suppress colorectal cancer cell proliferation via miR-10a/miR-143/miR-217/miR-512-mediated regulation of PI3K/AKT and Wnt/β-catenin signaling pathways

Emerging evidence has shown lncRNAs play important roles in signaling pathways involved in colorectal cancer (CRC) carcinogenesis. However, only a few functional lncRNAs have been extensively researched, especially in CRC-related signaling pathways. Looking for novel candidate regulators of CRC incidence and progression, using available RNA-seq and microarray datasets, LINC00963 was introduced as a bona fide oncogenic-lncRNA. Consistently, RT-qPCR results showed that LINC00963 was up-regulated in CRC tissues. However, our attempt to amplify the full-length lncRNA from cDNA resulted in the discovery of two novel variants (LINC00963-v2 & LINC00963-v3) that surprisingly, were downregulated in CRC tissues, detected by RT-qPCR. Overexpression of LINC00963-v2/-v3 in HCT116 and SW480 cells resulted in downregulation of the major oncogenes and upregulation of the main tumor suppressor genes involved in PI3K and Wnt signaling, verified through RT-qPCR, western blotting, and TOPFlash assays. Mechanistic studies revealed that LINC00963-v2/-v3 exert their effect on PI3K and Wnt signaling through sponging miR-10a-5p, miR-143-3p, miR-217, and miR-512-3p, which in turn these miRNAs are fine-regulators of PTEN, APC1, and Axin1 tumor suppressor genes verified by dual-luciferase assay and RT-qPCR. At cellular levels, LINC00963-v2/-v3 overexpression suppressed cell proliferation, viability, and migration while increasing the apoptosis of CRC cell lines, detected by PI flow cytometry, colony formation, MTT, RT-qPCR, wound-healing, Transwell, AnnexinV-PE/7AAD, caspase3/7 activity assays, and Hoechst/PI-AO/EB staining. Overall, our results indicate that LINC00963-v2 & -v3 are novel tumor suppressor ceRNAs that attenuate the PI3K and Wnt pathways during CRC incidence and these lncRNAs may serve as potential targets for CRC therapy.     

Long noncoding RNA LINC00629 restrains the progression of gastric cancer by upregulating AQP4 through competitively binding to miR-196b-5p

Gastric cancer continues to be a common cancer in the world with high incidence and mortality. Accumulating evidence has implicated long noncoding RNAs (lncRNAs) in gastric cancer progression. Here, this study identified the potential role of a novel lncRNA, LINC00629 in gastric cancer and to elucidate the underlying mechanism. Initially, microarray-based gene expression profiling of gastric cancer was employed to identify differentially expressed genes. Next, the expression of LINC00629, microRNA-196b-5p (miR-196b-5p) and aquaporin 4 (AQP4) in clinical gastric cancer tissues was determined and the cell line presenting with the lowest LINC00629 expression was selected. The interaction among LINC00629, miR-196b-5p, and AQP4 was identified. Expression of LINC00629, miR-196b-5p, and AQP4 in gastric cancer cells were altered and then biological behaviors of gastric cancer cells were assessed by 5-ethynyl-2′-deoxyuridine and Transwell assays. Tumor formation in vivo was evaluated in nude mice. In gastric cancer, expression of LINC00629 and AQP4 was downregulated, and expression of miR-196b-5p was upregulated. Proliferation, invasion, and migration of gastric cancer cells were reduced after overexpression of LINC00629. LINC00629 competitively bound to miR-196b-5p, while AQP4 was a target of miR-196b-5p. Either downregulating miR-196b-5p or upregulating AQP4 could restrain the development of gastric cancer in vitro. LINC00629 overexpression repressed the growth of transplanted tumors in vivo. Taken together, LINC00629 competitively bound to miR-196b-5p to upregulate AQP4 expression, thereby inhibiting gastric cancer progression. Therefore, understanding of this mechanism may help to improve gastric cancer treatment.     

Inhibition of PTEN Gene Expression by Oncogenic miR-23b-3p in Renal Cancer

Background

miR-23b is located on chromosome number 9 and plays different roles in different organs especially with regards to cancer development. However, the functional significance of miR-23b-3p in renal cell carcinoma (RCC) has not been reported.

Methods and Results

We measured miR-23b-3p levels in 29 pairs of renal cell carcinoma and their normal matched tissues using real-time PCR. The expression level of miR-23b-3p was correlated with the 5 year survival rate of renal cancer patients. In 15 cases (52%), miR-23b-3p expression was found to be high. All patients with moderate to low miR-23b-3p expression survived 5 years, while those with high miR-23b-3p expression, only 50% survived. After knocking down miRNA-23b-3p expression in RCC cell lines, there was an induction of apoptosis and reduced invasive capabilities. MiR-23b-3p was shown to directly target PTEN gene through 3′UTR reporter assays. Inhibition of miR-23b-3p induces PTEN gene expression with a concomitant reduction in PI3-kinase, total Akt and IL-32. Immunohistochemistry showed the lack of PTEN protein expression in cancerous regions of tissue samples where the expression of miR-23b-3p was high. We studied the in vitro effects of the dietary chemo preventive agent genistein on miR-23b-3p expression and found that it inhibited expression of miR-23b-3p in RCC cell lines.

Conclusions

The current study shows that miR-23b-3p is an oncogenic miRNA and inhibits PTEN tumor suppressor gene in RCC. Therefore, inhibition of miR-23b-3p may be a useful therapeutic target for the treatment of renal cell carcinoma.     

下调lncRNA MCF2L-AS1靶向miR-33b-5p抑制胃癌细胞增殖、迁移、侵袭并促进凋亡

摘要 目的：探讨lncRNA MCF2L-AS1对胃癌细胞恶性生物学行为的影响及分子机制。方法：选取45例胃癌患者的癌组织及癌旁正常组织,或培养胃黏膜上皮细胞GES-1、胃癌细胞HGC-27,采用RT-qPCR检测MCF2L-AS1和miR-33b-5p的表达水平。采用双荧光素酶报告实验检测MCF2L-AS1和miR-33b-5p的靶向关系。将HGC-27细胞分为si-NC组、si-MCF2L-AS1组、mimic NC组、miR-33b-5p mimic组、si-MCF2L-AS1+inhibitor NC组、si-MCF2L-AS1+miR-33b-5p inhibitor组,分别转染si-NC、si-MCF2L-AS1、mimic NC、miR-33b-5p mimic或共转染si-MCF2L-AS1+inhibitor NC、si-MCF2L-AS1+miR-33b-5p inhibitor。采用MTT实验检测细胞增殖情况,流式细胞术检测细胞凋亡率,克隆形成实验检测细胞克隆形成数,Transwell实验检测迁移和侵袭细胞数。结果：与癌旁正常组织或GES-1细胞相比,胃癌组织或HGC-27细胞中MCF2L-AS1表达水平升高、miR-33b-5p表达水平降低,差异均有统计学意义（P<0.05）。MCF2L-AS1可靶向调控miR-33b-5p。下调MCF2L-AS1或过表达miR-33b-5p,miR-33b-5p表达水平升高,HGC-27细胞凋亡率升高,但细胞增殖、克隆形成数、迁移和侵袭数均减少,差异均有统计学意义（P<0.05）。抑制miR-33b-5p可减弱下调MCF2L-AS1对HGC-27细胞的生物学作用。结论：下调MCF2L-AS1通过上调miR-33b-5p抑制胃癌细胞增殖、迁移、侵袭并促进凋亡;MCF2L-AS1通过靶向调控miR-33b-5p表达进而参与胃癌细胞的恶性生物学行为。     

Long non-coding RNA 657 suppresses hepatocellular carcinoma cell growth by acting as a molecular sponge of miR-106a-5p to regulate PTEN expression

Previous study has identified the aberrant expression of LINC00657, a long non-coding RNA (lncRNA), in human breast cancer. However, the expression pattern, biological function and underlying mechanism of LINC00657 in human hepatocellular carcinoma (HCC) remain obscure. The expression levels of LINC00657 in HCC tissues and cell lines were determined by quantitative real-time PCR. CCK-8 assay, cell colony formation assay, cell cycle analysis, Transwell assay were performed to determine whether LINC00657 could affect HCC progression. Luciferase reporter assay was used to assess the target of LINC00657. Expressions of the relevant proteins were analyzed by Western blot. Herein, we found that LINC00657 was downregulated in HCC tissue specimens as well as in malignant HCC cell lines. LINC00657 overexpression inhibited the proliferation, migration and invasion of HCC cells, while LINC00657 depletion promoted both cell viability and cell invasion in vitro. We also found that LINC00657 could inhibit tumor growth in vivo. Further experiments demonstrated that down-regulated LINC00657 increased the expression of miR-106a-5p. miR-106a-5p decreased the abundances of PTEN protein, while had no impact on PTEN mRNA. Moreover, we identified that both LINC00657 and PTEN mRNA were targets of miR-106a-5p by using dual-luciferase reporter assay. Our results provide the new evidence supporting the tumor-suppressive role of LINC00657 in HCC, suggesting that LINC00657 might play a role in HCC and can be a novel therapeutic target for treating HCC.     

LncRNA PDCD4-AS1 alleviates triple negative breast cancer by increasing expression of IQGAP2 via miR-10b-5p

ObjectiveMounting evidence demonstrates that long non-coding RNA (lncRNA) is dysregulated in breast cancers. This study was designed to detect the influences and regulatory mechanism of lncRNA PDCD4-AS1 in triple-negative breast cancer (TNBC).MethodsqRT-PCR and Western blot were utilized to investigate the expression levels of PDCD4-AS1, miR-10b-5p and IQGAP2 in TNBC tissues and cells. Online software and luciferase reporter gene system were employed to testify the interactions among these molecules. Loss and gain of function of PDCD4-AS1, miR-10b-5p or IQGAP2 were performed before MTT and colony formation assay, TUNEL staining in addition to Transwell and scratch assays were applied to measure the cell biological functions.ResultsIn this work, PDCD4-AS1 and IQGAP2 were lowly expressed while miR-10b-5p was strongly expressed in TNBC tissues and cells. PDCD4-AS1 or IQGAP2 overexpression effectively attenuated TNBC cell proliferation, migration and invasion, and increased the apoptosis rate, while this effect was abandoned in response to miR-10b-5p mimics transfection. miR-10b-5p bound to IQGAP2 and acted as a downstream target of PDCD4-AS1.ConclusionOur findings identified lncRNA PDCD4-AS1 as a tumor suppressor in TNBC by regulating IQGAP2 expression via miR-10b-5p, giving a novel insight into the regulatory mechanism of PDCD4-AS1 in the pathogenesis of TNBC.     

miR-424-5p regulates apoptosis and cell proliferation via targeting Bcl2 in nucleus pulposus cells

ABSTRACT

miRNAs play an important role in the pathogenesis of intervertebral disc degeneration (IDD). The role and the underlying mechanism of miR-424-5p in human nucleus pulposus (NP) are still unknown. We aimed to explore the role of miR-424-5p in IDD.

Real-time PCR was used to detect the expression of miR-424-5p and Bcl2 in IDD tissues and idiopathic scoliosis tissues. Human NP cells were used in our study. MTT and Hoechst apoptosis assays were used to detect the proliferation and apoptosis of NP cells, respectively. Western blotting assays were used to detect the expression levels of Bcl-2, cleaved caspase-3, cleaved caspase-9, caspase-3 and caspase-9 in degenerative NP cells. A luciferase reporter assay was applied to confirm the relationship between miR-424-5p and Bcl2.

Our results showed that the expression of miR-424-5p was increased and Bcl2 was decreased in degenerative NP cells. miR-425-5p expression was negatively correlated with Bcl2 expression in IDD tissues. Suppression of miR-424-5p using an inhibitor increased Bcl2 expression at both the mRNA and protein levels, and it promoted cell viability and inhibited apoptosis. Furthermore, the levels of cleaved caspase-3 and cleaved caspase-9 were downregulated in miR-424-5p-silenced NP cells. Interestingly, we found that silencing miR-424-5p increased p62 expression at both the mRNA and protein levels. Finally, a luciferase reporter assay verified the binding of the miR-424-5p and the 3’UTR of Bcl2.

These results suggested that silencing miR-424-5p suppressed NP cell apoptosis by upregulating Bcl2. Therefore, miR-424-5p might be a novel target for IDD therapies.     

MicroRNA-146b-5p promotes atrial fibrosis in atrial fibrillation by repressing TIMP4

Alteration of tissue inhibitors of matrix metalloproteinases (TIMP)/matrix metalloproteinases (MMP) associated with collagen upregulation has an important role in sustained atrial fibrillation (AF). The expression of miR-146b-5p, whose the targeted gene is TIMPs, is upregulated in atrial cardiomyocytes during AF. This study was to determine whether miR-146b-5p could regulate the gene expression of TIMP4 and the contribution of miRNA to atrial fibrosis in AF. Collagen synthesis was observed after miR-146b-5p transfection in human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs)-fibroblast co-culture cellular model in vitro. Furthermore, a myocardial infarction (MI) mouse model was used to confirm the protective effect of miR-146b-5p downregulation on atrial fibrosis. The expression level of miR-146b-5p was upregulated, while the expression level of TIMP4 was downregulated in the fibrotic atrium of canine with AF. miR-146b-5p transfection in hiPSC-aCMs-fibroblast co-culture cellular model increased collagen synthesis by regulating TIMP4/MMP9 mediated extracellular matrix proteins synthesis. The inhibition of miR-146b-5p expression reduced the phenotypes of cardiac fibrosis in the MI mouse model. Fibrotic marker MMP9, TGFB1 and COL1A1 were significantly downregulated, while TIMP4 was significantly upregulated (at both mRNA and protein levels) by miR-146b-5p inhibition in cardiomyocytes of MI heart. We concluded that collagen fibres were accumulated in extracellular space on miR-146b-5p overexpressed co-culture cellular model. Moreover, the cardiac fibrosis induced by MI was attenuated in antagomiR-146 treated mice by increasing the expression of TIMP4, which indicated that the inhibition of miR-146b-5p might become an effective therapeutic approach for preventing atrial fibrosis.     

Long noncoding RNA LINC00473 drives the progression of pancreatic cancer via upregulating programmed death-ligand 1 by sponging microRNA-195-5p

Pancreatic cancer (PC) is a great health burden to patients owing to its poor overall survival rate. Long noncoding RNAs (lncRNAs) interact with microRNAs (miRs) to participate in tumorigenesis. Therefore, we aim to uncover the role and related mechanism of LINC00473 in PC through the modulation of miR-195-5p and programmed death-ligand 1 (PD-L1). Increased LINC00473 and PD-L1 but declined miR-195-5p were determined in PC tissues and cell lines, and it was found that LINC00473 mainly situated in the cytoplasm. Also, miR-195-5p was verified to bind with both LINC00473 and PD-L1. Next, with the aim to examine the ability of LINC00473, miR-195-5p, and PD-L1 on the PC progression, the expression of LINC00473, miR-195-5p and PD-L1 were altered with mimics, inhibitors, overexpression vectors or siRNAs in PC cells and cocultured CD8⁺ T cells. It was demonstrated that LINC00473 sponged miR-195-5p to upregulate PD-L1 expression. More important, the obtained results revealed that LINC00473 silencing or miR-195-5p upregulation elevated the expression of Bcl-2 associated X protein (Bax), interferon (IFN)-γ, and interleukin (IL)-4 but reduced the expression of B-cell lymphoma-2 (Bcl-2), matrix metalloproteinase (MMP)-2, MMP-9, and IL-10, thus inducing the enhancement of the apoptosis as along with the inhibition of proliferation, invasion, and migration of the PC cells. LINC00473 silencing or miR-195-5p elevation activated the CD8⁺ T cells. Taken together, LINC00473 silencing blocked the PC progression through enhancing miR-195-5p-targeted downregulation of PD-L1. This finding offers new therapeutic options for treating this devastating disease.     

A potential regulatory network among WDR86-AS1, miR-10b-3p,and LITAF is possibly involved in preeclampsia pathogenesis

Preeclampsia (PE), a pregnancy-specific disorder, is a leading cause of perinatal maternal and fetal mortality and morbidity. Impaired migration and invasion of trophoblastic cells and an imbalanced systemic maternal inflammatory response have been proposed as possible causes of pathogenesis of PE. Comparative analysis of PE-affected placentas and healthy placentas has uncovered differentially expressed long noncoding RNAs, microRNAs, and mRNAs. This study was conducted to investigate the effect of a regulatory network among these RNAs on PE pathogenesis. Long noncoding RNA WDR86-AS1, microRNA miR-10b-3p, and mRNA of protein LITAF were identified by screening of genes in existing databases with aberrant expression in PE-affected placentas and potential mutual interactions as revealed by TargetScan, miRanda, and PicTar analyses. This study identified their expression in PE-affected and healthy placentas by RT-PCR. An in vitro experiment was performed on human trophoblast HTR-8/SVneo cells cultured under normoxic or hypoxic conditions. MiR-10b-3p targets were identified in luciferase reporter assays and RNA pull-down assays. The mouse model of PE was set up using a soluble form of FLT-1 for in vivo testing. Lower levels of miR-10b-3p but higher expression of WDR86-AS1 and LITAF were observed in PE-affected placentas and trophoblast cells under hypoxia. WDR86-AS1 and LITAF mRNA were confirmed as targets of miR-10b-3p. WDR86-AS1 downregulated miR-10b-3p but promoted LITAF expression. Microarray analyses revealed that LITAF controlled the inflammatory responses and migration and proliferation of HTR-8/SVneo cells under hypoxia. Indeed, knockdown of WDR86-AS1 and LITAF or overexpression of miR-10b-3p attenuated the hypoxia-induced inhibition of cellular viability, migration, and invasion. Moreover, miR-10b-3p overexpression attenuated the pathological symptoms caused by soluble FLT-1 in vivo. In summary, the WDR86-AS1/miR-10b-3p/LITAF network is probably involved in PE pathogenesis.