The (pro)renin receptor [(P)RR, ATP6AP2] is a multifunctional transmembrane protein that activates local renin-angiotensin systems, but also interacts with Wnt pathways and vacuolar H+ -ATPase (V-ATPase) during organogenesis. The aim of this study was to characterize the role of ATP6AP2 in the cell cycle in more detail. ATP6AP2 down-regulation by siRNA in renal As4.1 cells resulted in a reduction in the rate of proliferation and a G0/G1 phase cell cycle arrest. We identified a number of novel target genes downstream of ATP6AP2 knock-down that were related to the primary cilium (Bbs-1, Bbs-3, Bbs-7, Rabl5, Ttc26, Mks-11, Mks-5, Mks-2, Tctn2, Nme7) and the cell cycle (Pierce1, Clock, Ppif). Accordingly, the number of cells expressing the primary cilium was markedly increased. We found no indication that these effects were dependent of V-ATPase activity, as ATP6AP2 knock-down did not affect lysosomal pH and bafilomycin A neither influenced the ciliary expression pattern nor the percentage of ciliated cells. Furthermore, ATP6AP2 appears to be essential for mitosis. ATP6AP2 translocated from the endoplasmatic reticulum to mitotic spindle poles (pro-, meta- and anaphase) and the central spindle bundle (telophase) and ATP6AP2 knock-down results in markedly deformed spindles. We conclude that ATP6AP2 is necessary for cell division, cell cycle progression and mitosis. ATP6AP2 also inhibits ciliogenesis, thus promoting proliferation and preventing differentiation.

Our recent study showed that bradykinin increases cell cycling progression and migration of human cardiac c-Kit+ progenitor cells by activating pAkt and pERK1/2 signals. This study investigated whether bradykinin-mediated Ca2+ signalling participates in regulating cellular functions in cultured human cardiac c-Kit+ progenitor cells using laser scanning confocal microscopy and biochemical approaches. It was found that bradykinin increased cytosolic free Ca2+ ( Cai2+ ) by triggering a transient Ca2+ release from ER IP3Rs followed by sustained Ca2+ influx through store-operated Ca2+ entry (SOCE) channel. Blockade of B2 receptor with HOE140 or IP3Rs with araguspongin B or silencing IP3R3 with siRNA abolished both Ca2+ release and Ca2+ influx. It is interesting to note that the bradykinin-induced cell cycle progression and migration were not observed in cells with siRNA-silenced IP3R3 or the SOCE component TRPC1, Orai1 or STIM1. Also the bradykinin-induced increase in pAkt and pERK1/2 as well as cyclin D1 was reduced in these cells. These results demonstrate for the first time that bradykinin-mediated increase in free Cai2+ via ER-IP3R3 Ca2+ release followed by Ca2+ influx through SOCE channel plays a crucial role in regulating cell growth and migration via activating pAkt, pERK1/2 and cyclin D1 in human cardiac c-Kit+ progenitor cells.

Cells derived from the amniotic foetal membrane of human term placenta have drawn particular attention mainly for their plasticity and immunological properties, which render them interesting for stem-cell research and cell-based therapeutic applications. In particular, we have previously demonstrated that amniotic mesenchymal tissue cells (AMTC) inhibit lymphocyte proliferation in vitro and suppress the generation and maturation of monocyte-derived dendritic cells. Here, we show that AMTC also significantly reduce the proliferation of cancer cell lines of haematopoietic and non-haematopoietic origin, in both cell-cell contact and transwell co-cultures, therefore suggesting the involvement of yet-unknown inhibitory soluble factor(s) in this 'cell growth restraint'. Importantly, we provide evidence that the anti-proliferative effect of AMTC is associated with induction of cell cycle arrest in G0/G1 phase. Gene expression analyses demonstrate that AMTC can down-regulate cancer cells' mRNA expression of genes associated with cell cycle progression, such as cyclins (cyclin D2, cyclin E1, cyclin H) and cyclin-dependent kinase (CDK4, CDK6 and CDK2), whilst they up-regulate cell cycle negative regulator such as p15 and p21, consistent with a block in G0/G1 phase with no progression to S phase. Taken together, these findings warrant further studies to investigate the applicability of these cells for controlling cancer cell proliferation in vivo.

WD-repeat protein 79 (WDR79), a member of the WD-repeat protein family, acts as a scaffold protein, participating in telomerase assembly, Cajal body formation and DNA double-strand break repair. Here, we first report that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung cancer (NSCLC). Knockdown of WDR79 significantly inhibited the proliferation of NSCLC cells in vitro and in vivo by inducing cell cycle arrest and apoptosis. WD-repeat protein 79 -induced cell cycle arrest at the G0/G1 phase was associated with the expression of G0/G1-related cyclins and cyclin-dependent kinase complexes. We also provide evidence that WDR79 knockdown induces apoptosis via a mitochondrial pathway. Collectively, these results suggest that WDR79 is involved in the tumorigenesis of NSCLC and is a potential novel diagnostic marker and therapeutic target for NSCLC.

Melatonin exhibits antitumour activities in the treatment of many human cancers. In the present study, we aimed to improve the therapeutic potential of melatonin in gastric cancer. Our results confirmed that melatonin dose-dependently suppressed the proliferation and necrosis, and increased G0/G1 phase arrest, apoptosis, autophagy and endoplasmic reticulum (ER) stress. The Ras-Raf-MAPK signalling pathway was activated in cells after melatonin treatment. RNA-seq was performed and GSEA analysis further confirmed that many down-regulated genes in melatonin-treated cells were associated with proliferation. However, GSEA analysis also indicated that many pathways related to metastasis were increased after melatonin treatment. Subsequently, combinatorial treatment was conducted to further investigate the therapeutic outcomes of melatonin. A combination of melatonin and thapsigargin increased the apoptotic rate and G0/G1 cell cycle arrest when compared to treatment with melatonin alone. Melatonin in combination with thapsigargin triggered the increased expression of Bip, LC3-II, phospho-Erk1/2 and phospho-p38 MAPK. In addition, STF-083010, an IRE1a inhibitor, further exacerbated the decrease in survival rate induced by combinatorial treatment with melatonin and thapsigargin. Collectively, melatonin was effective in gastric cancer treatment by modifying ER stress.

In this study, our aim was to exploring the influences of DNA methylation of PON1 on cell proliferation, migration and apoptosis of renal cancer cells. The genome-wide methylation array of renal cell carcinoma samples and adjacent tissues were obtained from the cancer genome atlas (TCGA) database. By analysing the DNA methylation and conducting the CpG islands array, methylation status expressed in renal tumour samples and normal renal tissue samples were detected. Methylation-specific PCR (MS-PCR) and qRT-PCR were employed to detect the methylation level and mRNA expression of PON1. Wound-healing assay, transwell assay and MTT assay were utilized to detecting the migration, invasion and proliferation abilities, respectively. The cell apoptosis was testified by Tunnel assay. In addition, the effect of PON1 on renal cancer cells was verified by experiments in vivo. The methylation status of different genes in renal cell carcinoma samples was obtained by CpG islands arrays and hypermethylated PON1 was selected for further study. PON1 was down-regulated in renal cell carcinoma tissues detected by qRT-PCR and Western blot. Both in vitro and vivo experiments indicated that the sunitinib-resistant in renal cancer cells could be suppressed by treat with 5-Aza-dC or TSA, and the effect came out more obvious after 5-Aza-dC and TSA co-treatment. In detail, the demethylation of PON1 inhibited the migration, invasion and proliferation of renal cancer cells and also arrested more cells in G0/G1 phase. The vivo experiment indicated that demethylated PON1 suppressed the growth of tumour. Hypermethylated PON1 promoted migration, invasion and proliferation of sunitinib-resistance renal cancer cells and arrested more cells in G0/G1 phase.

Pax3 and Pax7 are closely related transcription factors that are widely expressed in the developing nervous system and somites. During the normal development in the central nervous system (CNS), Pax3 and Pax7 are mainly expressed in the dorsal part of the neural tube. Further analysis revealed that Pax3 and Pax7 shared redundant functions in the spinal cord development. However, it is still unknown whether Pax3 and Pax7 play a role in neuronal differentiation. In this study, Pax3 and Pax7 genes were overexpressed in Neuro-2a, the mouse neuroblastoma cell line. CCK-8 and EdU assay results showed that overexpression of Pax3 inhibited cell viability and proliferation of Neuro-2a cells, whereas the overexpression of Pax7 had no significant difference on their cell viability and proliferation. Overexpression of Pax3 not only increased the percentage of cells in the S phase and G0/G1 phase, but also decreased that in the G2 phase. Moreover, the total neurite lengths of Neuro-2a cells were significantly shorter in Pax3 overexpressed group than those in negative control group and showed no significant difference between Pax7 overexpressed group and negative control group. These results suggested that Pax3 not only inhibited the cell viability and proliferation but also affected the cell cycle and the neurite outgrowth of Neuro-2a cells. RNA sequencing analysis showed up-regulated genes in Pax3 overexpressed group were involved in cell cycle machinery, which may reveal the potential mechanism of Neuro-2a cells proliferation.

Neuroblastoma is the second most common solid tumour during childhood, characterized by rapid disease progression. Most children with metastasized neuroblastoma die despite intensive chemotherapy due to an intrinsic or acquired chemotherapy resistance. Thus, new therapeutic strategies are urgently needed. Here, we demonstrate that the novel compound nemorosone isolated from alcoholic extracts of Clusia rosea resins by reverse phase high pressure liquid chromatography (RP-HPLC) exerts cytotoxic activity in neuroblas-toma cell lines both parental and their clones selected for resistance against adriamycin, cisplatin, etoposide or 5-fluorouracil. Cell cycle studies revealed that nemorosone induces an accumulation in G0/G1- with a reduction in S-phase population combined with a robust up-regulation of p21Cip1. Furthermore, a dose-dependent apoptotic DNA laddering accompanied by an activation of caspase-3 activity was detected. Nemorosone induced a significant dephosphorylation of ERK1/2 in LAN-1 parental cells probably by the inhibition of its upstream kinase MEK1/2. No significant modulation of signal transducers JNK, p38 MAPK and Akt/PKB was detected. The enzymatic activity of immunoprecipitated Akt/PKB was strongly inhibited in vitro, suggesting that nemorosone exerts its anti-proliferative activity at least in part by targeting Akt/PKB in the cell lines studied. In addition, a synergistic effect with Raf-1 inhibitor BAY 43-9006 was found. Finally, nemorosone induced a considerable down-regulation of N-myc protein levels in parental LAN-1 and an etoposide resistant sub-line at the same drug-concentrations.

Several clinical and experimental studies have demonstrated that regular use of aspirin (acetylsalicylic acid, ASA) correlates with a reduced risk of cancer and that the drug exerts direct anti-tumour effects. We have previously reported that ASA inhibits proliferation of human glioblastoma multiforme-derived cancer stem cells. In the present study, we analysed the effects of ASA on nervous system-derived cancer cells, using the SK-N-SH (N) human neuroblastoma cell line as an experimental model. ASA treatment of SK-N-SH (N) dramatically reduced cell proliferation and motility, and induced neuronal-like differentiation, indicated by the appearance of the neuronal differentiation marker tyrosine hydroxylase (TH) after 5 days. ASA did not affect cell viability, but caused a time-dependent accumulation of cells in the G0 /G1 phase of the cell cycle, with a concomitant decrease in the percentage of cells in the G2 phase. These effects appear to be mediated by a COX-independent mechanism involving an increase in p21Waf1 and underphosphorylated retinoblastoma (hypo-pRb1) protein levels. These findings may support a potential role of ASA as adjunctive therapeutic agent in the clinical management of neuroblastoma.

It is well-established that homocysteine (Hcy) is an independent risk factor for atherosclerosis. Hcy can promote vascular smooth muscle cell (VSMC) proliferation, it plays a key role in neointimal formation and thus contribute to arteriosclerosis. However, the molecular mechanism on VSMCs proliferation underlying atherosclerosis is not well elucidated. Mitofusin-2 (MFN2) is an important transmembrane GTPase in the mitochondrial outer membrane and it can block cells in the G0/G1 stage of the cell cycle. To investigate the contribution of aberrant MFN2 transcription in Hcy-induced VSMCs proliferation and the underlying mechanisms. Cell cycle analysis revealed a decreased proportion of VSMCs in G0/G1 and an increased proportion in S phase in atherosclerotic plaque of APOE-/- mice with hyperhomocystinaemia (HHcy) as well as in VSMCs exposed to Hcy in vitro. The DNA methylation level of MFN2 promoter was obviously increased in VSMCs treated with Hcy, leading to suppressed promoter activity and low expression of MFN2. In addition, we found that the expression of c-Myc was increased in atherosclerotic plaque and VSMCs treated with Hcy. Further study showed that c-Myc indirectly regulates MFN2 expression is duo to the binding of c-Myc to DNMT1 promoter up-regulates DNMT1 expression leading to DNA hypermethylation of MFN2 promoter, thereby inhibits MFN2 expression in VSMCs treated with Hcy. In conclusion, our study demonstrated that Hcy-induced hypermethylation of MFN2 promoter inhibits the transcription of MFN2, leading to VSMCs proliferation in plaque formation, and the increased binding of c-Myc to DNMT1 promoter is a new and relevant molecular mechanism.

This study aimed to determine the interactions between parathyroid hormone type 1 receptor (PTHR1) and angiotensinogen (AGT) and the effects of these agents on osteosarcoma (OS). We constructed a stably transfected mouse OS K7M2 cell line (shPTHR1- K7M2) using shRNA and knocked down AGT in these cells using siRNA-AGT. The transfection efficiency and expression of AGT, chemokine C-C motif receptor 3 (CCR3), and chemokine (C-C motif) ligand 9 (CCL9) were determined using real-time quantitative PCR. Cell viability and colony formation were assessed using Cell Counting Kit-8 and crystal violet staining, respectively. Cell apoptosis and cycle phases were assessed by flow cytometry, and cell migration and invasion were evaluated using Transwell assays. Interference with PTHR1 upregulated the expression of AGT and CCR3, and downregulated that of CCL9, which was further downregulated by AGT knockdown. Cell viability, migration, invasion and colony formation were significantly decreased, while cell apoptosis was significantly increased in shPTHR1-K7M2, compared with those in K7M2 cells (P < .05 for all). However, AGT knockdown further inhibited cell viability after 72 h of culture but promoted cell migration and invasion. PTHR1 interference decreased and increased the numbers of cells in the G0/G1 and G2/M phases, respectively, compared with those in K7M2 cells. Angiotensinogen knockdown increased the number of cells in the G0/G1 phase compared with that in the shPTHR1-K7M2 cells. Therefore, PTHR1 affects cell viability, apoptosis, migration, invasion and colony formation, possibly by regulating AGT/CCL9 in OS cells.

Long non-coding ribonucleic acids (lncRNAs) play critical roles in acute lung injury (ALI). We aimed to explore the involvement of lncRNA HOX transcript antisense intergenic ribonucleic acid (HOTAIR) in regulating autophagy in lipopolysaccharide (LPS)-induced ALI. We obtained 1289 differentially expressed lncRNAs or messenger RNAs (mRNAs) via microarray analysis. HOTAIR was significantly upregulated in the LPS stimulation experimental group. HOTAIR knockdown (si-HOTAIR) promoted cell proliferation in LPS-stimulated A549 and BEAS-2B cells, suppressing the protein expression of autophagy marker light chain 3B and Beclin-1. Inhibition of HOTAIR suppressed LPS-induced cell autophagy, apoptosis and arrested cells in the G0/G1 phase prior to S phase entry. Further, si-HOTAIR alleviated LPS-induced lung injury in vivo. We predicted the micro-ribonucleic acid miR-17-5p to target HOTAIR and confirmed this via RNA pull-down and dual luciferase reporter assays. miR-17-5p inhibitor treatment reversed the HOTAIR-mediated effects on autophagy, apoptosis, cell proliferation and cell cycle. Finally, we predicted autophagy-related genes (ATGs) ATG2, ATG7 and ATG16 as targets of miR-17-5p, which reversed their HOTAIR-mediated protein upregulation in LPS-stimulated A549 and BEAS-2B cells. Taken together, our results indicate that HOTAIR regulated apoptosis, the cell cycle, proliferation and autophagy through the miR-17-5p/ATG2/ATG7/ATG16 axis, thus driving LPS-induced ALI.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor family of ligand-activated transcription factors and plays an important role in regulating cell proliferation, inflammation and lipid and glucose homeostasis. Our results revealed that PPARγ was up-regulated in human bladder cancer (BCa) tissues both at transcriptional and translational levels. Moreover, down-regulation of PPARγ mRNA or inhibition of PPARγ function (using GW9662, antagonist of PPARγ) could significantly suppress the proliferation of BCa cells. Furthermore, the cell cycle arrested in G0/G1 phase was also induced by the down-regulated PPARγ possibly through AKT-mediated up-regulation of p21/p27, whereas no significant transformation of apoptosis was observed. In addition, knockdown or inhibition of PPARγ might reduce the invasion and migration of BCa cells by affecting epithelial-mesenchymal transition-related proteins through AKT/GSK3β signalling pathway. Additionally, in vivo studies showed that BCa cell proliferation was significantly suppressed by GW9662. In conclusion, our results indicated that PPARγ might be crucial for BCa tumorigenesis by interfering with the motility and viability of BCa cells.

This study is aimed to investigate the methylation level of candidate genes and its impact on thyroid carcinoma (THCA) development. Infinium Human Methylation 450 BeadChip Arrays by Illumina (Illumina HM450K) was the most popular CpG microarray platform widely used in biological and medical research. The methylation level of differentially expressed genes and their corresponding CpG sites were analysed by R programme. The expression of HORMAD2 was evaluated by qRT-PCR and Western blot, while the methylation level was examined via methylation-specific PCR. Cell viability, metastasis, cell cycle and apoptosis were detected by MTT assay, transwell and wound healing assay and flow cytometry, respectively, after treatment with 5-aza-2'-deoxycytidine (5-Aza). Tumour formation assay was used to analyse thyroid tumour growth in nude mice in vivo. The methylation levels of all 116 differentially expressed genes were analysed. HORMAD2 was significantly hypermethylated and its mRNA expression was inhibited in THCA cells. After treatment with 5-Aza, HORMAD2 expression was up-regulated in THCA cells and its overexpression can suppress thyroid cancer cell viability, mobility and invasiveness remarkably. Up-regulation of HORMAD2 in THCA cells could prolong G0/G1 phase and shorten S phase to impede cell mitosis as well as promote thyroid cancer cells apoptosis. Furthermore, tumour formation assay showed that increased HORMAD2 level impeded tumour growth in vivo. Hypermethylation of HORMAD2 could induce THCA progression, while hypomethylation of HORMAD2 retard cell growth and mobility and facilitate apoptosis through increasing its mRNA expression.

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into a variety of cell types. Bortezomib, the first approved proteasome inhibitor used for the treatment of multiple myeloma (MM), has been shown to induce osteoblast differentiation, making it beneficial for myeloma bone disease. In the present study, we aimed to investigate the effects and underlying mechanisms of bortezomib on the cell cycle during osteogenic differentiation. We confirmed that low doses of bortezomib can induce MSCs towards osteogenic differentiation, but high doses are toxic. In the course of bortezomib-induced osteogenic differentiation, we observed cell cycle exit characterized by G0 /G1 phase cell cycle arrest with a significant reduction in cell proliferation. Additionally, we found that the cell cycle exit was tightly related to the induction of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 . Notably, we further demonstrated that the up-regulation of p21Cip1 and p27Kip1 is transcriptionally dependent on the bortezomib-activated ER stress signalling branch Ire1α/Xbp1s. Taken together, these findings reveal an intracellular pathway that integrates proteasome inhibition, osteogenic differentiation and the cell cycle through activation of the ER stress signalling branch Ire1α/Xbp1s.

Insulin-like growth factor-2 messenger RNA-binding protein 3 (IGF2BP3) has been reported to contribute to tumorigenesis in several human cancers. However, the biological functions of IGF2BP3 in bladder cancer are poorly understood. We investigated the relation between IGF2BP3 expression and prognosis of bladder cancer patients. Cell proliferation, cell cycle and cell apoptosis assays were performed to assess IGF2BP3 functions. The results showed that IGF2BP3 was overexpressed in bladder cancer tissues compared with that in normal bladder tissues, and its higher expression was closely correlated with poor prognosis in bladder cancer patients. Overexpression of IGF2BP3 markedly promoted cell proliferation and cell cycle progression and inhibited cell apoptosis, while knockdown of IGF2BP3 notably suppressed the proliferation, promoted cell apoptosis and induced cell cycle arrest at the G0/G1 phase. Mechanistically, we revealed that IGF2BP3 promotes the activation of the JAK/STAT pathway in bladder cancer cells. Moreover, the JAK/STAT inhibitor dramatically blocked the tumour-promoting activity of IGF2BP3. Tumour growth in vivo was also suppressed by knocking down of IGF2BP3. Hence, IGF2BP3 facilitated bladder cancer cell proliferation by activating the JAK/STAT signalling pathway. These findings suggest that IGF2BP3 exhibits an oncogenic effect in human bladder cancer progression.

This study aimed to explore the effects of CLIC1 gene silencing on proliferation, migration, invasion and apoptosis of human gallbladder cancer (GBC). GBC and normal gallbladder tissues were extracted for the detection of mRNA and protein expressions of CLIC1. GBC-SD and NOZ cells in the logarithmic growth phase were selected to conduct the experiment. Three different siRNA recombined expression vectors were established using CLIC1 as a target at different sites. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were, respectively, used to detect the CLIC1 mRNA and protein expressions. MTT assay was performed to detect the cell proliferation. Flow cytometry was applied to measure the cell apoptosis and cell cycle distribution. The variations of cell migration and invasion were evaluated using Transwell assay. GBC tissues showed higher CLIC1 mRNA and protein expressions than normal gallbladder tissues. The CLIC1 mRNA and protein expressions in the CLIC1 siRNA group were significantly lower than those in the NC and blank groups. Compared with the NC and blank groups, the CLIC1 siRNA group showed a significant decrease in cell proliferation but an obvious increase in apoptosis rate in GBC cells. Besides, in the CLIC1 siRNA group, cell percentage in G0/G1 and G2/M phase was gradually increased but decreased in S phases. The migration and invasion abilities in GBC cells were significantly lower than those in the NC and blank groups. Our study demonstrates that CLIC1 gene silencing could promote apoptosis and inhibit proliferation migration and invasion of GBC cells.

Farnesoid X receptor (FXR, encoded by NR1H4), a bile acid-activated nuclear receptor, is widely implicated in human tumorigenesis. The FXR agonist obeticholic acid (OCA) has preliminarily displayed tumour suppressor potential. However, the anticancer effects of this agent on colorectal cancer (CRC) remain unclear. In this study, the treatment of colon cancer cells with OCA inhibited cell proliferation and invasion in vitro, retarded tumour growth in vivo and prevented the G0 /G1 to S phase transition. Moreover, the expression of active caspase-3, p21 and E-cadherin was up-regulated and the expression of cyclin D1, c-Myc, vimentin, N-cadherin and MMP9 was down-regulated in OCA-treated colon cancer cells. Mechanistic studies indicated that OCA treatment suppressed the activity of JAK2/STAT3 pathway by up-regulating SOCS3 expression. Colivelin, an agonist of JAK2/STAT3 pathway, antagonized the tumour-suppressive effect of OCA on colon cancer cells. Dual-luciferase reporter and quantitative chromatin immunoprecipitation (qChIP) assays further confirmed that OCA promoted SOCS3 transcription by enhancing the binding of FXR to the FXRE/IR9 of the SOCS3 promoter. In conclusion, our study demonstrates that targeting FXR and improving its function might be a promising strategy for CRC treatment.

Long non-coding RNA Sox2 overlapping transcript (SOX2OT) was reported to be involved in progression of multiple cancers. However, the role and mechanism of SOX2OT in multiple myeloma (MM) has yet to be unravelled. In the present study, elevated SOX2OT levels are reported in MM cell lines and patient samples as compared to normal plasma cells (nPCs) and healthy donors, respectively. Knock-down of SOX2OT led to a significant inhibition of cell proliferation, arrested cells at G0/G1 phase and induced cell apoptosis in MM samples in vitro, as well as slowed the growth of tumours in vivo. Additionally, our data indicated that SOX2OT functioned as a competing endogenous RNA (ceRNA) in MM cells that regulated miR-144-3p expression. Repression of miR-144-3p reversed the inhibition of MM development due to SOX2OT knock-down. Our data also revealed that SOX2OT regulated the expression of the cellular-mesenchymal to epithelial transition factor (c-MET, a known target of miR-143-3p) by functioning as a sponge of miR-144-3p in MM samples. These data support that SOX2OT promotes MM progression through regulating the miR-144-3p/c-MET axis, suggesting that SOX2OT might be as a potential therapeutic target for MM.

Gliomas are the most common form of malignant tumour in the central nervous system. However, the molecular mechanism of the tumorigenesis and progression of gliomas remains unclear. In this study, we used the GEO database to identify genes differentially expressed in gliomas and predict the prognosis of glioma. We observed that ASPM mRNA was increased obviously in glioma tissue, and higher ASPM mRNA expression predicted worse disease prognosis. ASPM was highly expressed in glioma cell lines U87-MG and U251, and knockdown of ASPM expression in these cells significantly repressed the proliferation, migration and invasion ability and induced G0/G1 phase arrest. In addition, down-regulation of ASPM suppressed the growth of glioma in nude mice. Five potential binding sites for transcription factor FoxM1 were predicted in the ASPM promoter. FoxM1 overexpression significantly increased the expression of ASPM and promoted the proliferation and migration of glioma cells, which was abolished by ASPM ablation. ChIP and dual-luciferase reporter analysis confirmed that FoxM1 bound to the ASPM promoter at -236 to -230 bp and -1354 to -1348 bp and activated the transcription of ASPM directly. Collectively, our results demonstrated for the first time that aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the malignant properties of glioma cells.