Polymerized carbon dots with high electrochemiluminescence efficiency and long wavelength ECL emission for ultrasensitive detection of MicroRNA-222.

Herein, a new electrochemiluminescence (ECL) biosensor was constructed with highly efficient polymerized carbon dots (PCDs) as ECL emitter and the improved localized catalytic hairpin assembly (L-CHA) as signal amplifier for ultrasensitive detection of microRNA-222 (miRNA-222). Impressively, compared to the traditional carbon dots with inefficient blue region ECL emission, PCDs with N, O co-dope and large conjugated π-system showed high electrical conductivity, narrow band gap and strong radiative transition, which could exhibit high ECL efficiency to improve the sensitivity of detection and long wavelength ECL emission to achieve deep tissue penetration for reducing biological damage. Furthermore, the trace target miRNA-222 could be efficiently converted into large amounts of output DNA labelled with the quencher dopamine (S-DA) through the L-CHA reaction to significantly enhance the target amplification efficiency for further improving the sensitivity of detection. Thus, the ECL biosensor could achieve the ultrasensitive detection of miRNA-222 from 100 aM to 100 pM with the detection limit of 76 aM. Therefore, this work proposed a novel CDs with high ECL efficiency and long wavelength ECL emission, which not only was used to build an ultrasensitive biosensor for biomolecules detection in clinical diagnosis, but also served as a potential emitter for ECL bioimaging.

Renewable Electrochemiluminescence Biosensor Based on Eu-MOGs as a Highly Efficient Emitter and a DNAzyme-Mediated Dual-drive DNA Walker as a Signal Amplifier for Ultrasensitive Detection of miRNA-222.

Herein, novel europium metal-organic gels (Eu-MOGs) with excellent cathode electrochemiluminescence (ECL) emission are first used to construct biosensors for the ultrasensitive detection of miRNA-222. Impressively, N and O elements of organic ligand 2,2':6,2″-terpyridine 4,4',4″-tricarboxylic acid (H3-tctpy) can perfectly coordinate with Eu3+ to form Eu-MOGs, which not only reduce nonradiative transition caused by the intramolecular free rotation of phenyl rings in other MOGs to enhance the ECL signal with extraordinary ECL efficiency as high as 37.2% (vs the [Ru(bpy)3]2+/S2O82- ECL system) but also reinforce ligand-to-metal charge transfer (LMCT) by the strong affinity between Eu3+ and N and O elements to greatly improve the stability of ECL signals. Besides, an improved nucleic acid cascade amplification reaction is developed to greatly raise the conversion efficiency from target miRNA-222 to a DNAzyme-mediated dual-drive DNA walker as output DNA, which can simultaneously shear the specific recognition sites from two directions. In that way, the proposed biosensor can further enhance the detection sensitivity of miRNA-222 with a linear range of 10 aM-1 nM and a detection limit (LOD) of 8.5 aM, which can also achieve an accurate response in cancer cell lysates of MHCC-97L and HeLa. Additionally, the biosensor can be self-regenerated by the folding/unfolding of related triplets with pH changes to simplify experimental operations and reduce the cost. Hence, this work proposed novel MOGs with stable and intense ECL signals for the construction of a renewable ECL biosensor, supplying a reliable detection method in biomarker analysis and disease diagnosis.

Effect of high-fat diet on the fatty acid profiles of brain in offspring mice exposed to maternal gestational diabetes mellitus.

OBJECTIVE: Fatty acids play a critical role in the proper functioning of the brain. This study investigated the effects of a high-fat (HF) diet on brain fatty acid profiles of offspring exposed to maternal gestational diabetes mellitus (GDM). METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish the GDM animal model. Brain fatty acid profiles of the offspring mice were measured by gas chromatography at weaning and adulthood. Protein expressions of the fatty acid transport pathway Wnt3/ß-catenin and the target protein major facilitator superfamily domain-containing 2a (MFSD2a) were measured in the offspring brain by Western blot. RESULTS: Maternal GDM increased the body weight of male offspring (P < 0.05). In weaning offspring, factorial analysis showed that maternal GDM increased the monounsaturated fatty acid (MUFA) percentage of the weaning offspring's brain (P < 0.05). Maternal GDM decreased offspring brain arachidonic acid (AA), but HF diet increased brain linoleic acid (LA) (P < 0.05). Maternal GDM and HF diet reduced offspring brain docosahexaenoic acid (DHA), and the male offspring had higher DHA than the female offspring (P < 0.05). In adult offspring, factorial analysis showed that HF diet increased brain MUFA in offspring, and male offspring had higher brain MUFA than female offspring (P < 0.05). The HF diet increased brain LA in the offspring. Male offspring had higher level of AA than female offspring (P < 0.05). HF diet reduced DHA in the brains of female offspring. The brain protein expression of ß-catenin and MFSD2a in both weaning and adult female offspring was lower in the HF + GDM group than in the CON group (P < 0.05). CONCLUSIONS: Maternal GDM increased the susceptibility of male offspring to HF diet-induced obesity. HF diet-induced adverse brain fatty acid profiles in both male and female offspring exposed to GDM.

Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration.

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice.

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.

Effects of dietary PUFA patterns and FADS genotype on breast milk PUFAs in Chinese lactating mothers.

BACKGROUND: Breastfeeding affects the growth and development of infants, and polyunsaturated fatty acids (PUFAs) play a crucial role in this process. To explore the factors influencing the PUFA concentration in breast milk, we conducted research on two aspects: dietary fatty acid patterns and single nucleotide polymorphisms (SNPs) in maternal fatty acid desaturase genes. METHODS: Three hundred seventy Chinese Han lactating mothers were recruited. A dietary semi-quantitative food frequency questionnaire (FFQ) was used to investigate the dietary intake of lactating mothers from 22 to 25 days postpartum for 1 year. Meanwhile, breast milk samples were collected from the participants and tested for the concentrations of 8 PUFAs and 10 SNP genotypes. We sought to determine the effect of dietary PUFA patterns and SNPs on breast milk PUFAs. We used SPSS 24.0 statistical software for data analysis. Statistical tests were all bilateral tests, with P < 0.05 as statistically significant. RESULTS: Under the same dietary background, PUFA contents in breast milk expressed by most major allele homozygote mothers tended to be higher than that expressed by their counterparts who carried minor allele genes. Moreover, under the same gene background, PUFA contents in breast milk expressed by the mother's intake of essential PUFA pattern tended to be higher than that expressed by their counterparts who took the other two kinds of dietary. CONCLUSIONS: Our study suggests that different genotypes and dietary PUFA patterns affect PUFA levels in breast milk. We recommend that lactating mothers consume enough essential fatty acids to ensure that their infants ingest sufficient PUFAs.

Nitrogen-, Sulfur-, and Fluorine-Codoped Carbon Dots with Low Excitation Potential and High Electrochemiluminescence Efficiency for Sensitive Detection of Matrix Metalloproteinase-2.

In this study, nitrogen-, sulfur-, and fluorine-codoped carbon dots (NSF-CDs) with high electrochemiluminescence (ECL) efficiency were developed as novel emitters to fabricate an ECL biosensor for sensitive detection of matrix metalloproteinase 2 (MMP-2). Impressively, compared to previously reported CDs, NSF-CDs with narrow band gap not only decreased the excitation voltage to reduce the side reaction and the damage on biomolecules but also had hydrogen bonds to vastly enhance the ECL efficiency. Furthermore, an improved exonuclease III (Exo III)-assisted nucleic acid amplification method was established to convert trace MMP-2 into a mass of output DNA, which greatly improved the target conversion efficiency and ECL signal. Hence, the ECL biosensor has realized the sensitive detection of MMP-2 proteins from 10 fg/mL to 10 ng/mL with a limit of detection of 6.83 fg/mL and has been successfully applied in the detection of MMP-2 from Hela and MCF-7 cancer cells. This strategy offered neoteric CDs as ECL emitters for sensitive testing of biomarkers in medical research.

Polyphyllin II Induces Protective Autophagy and Apoptosis via Inhibiting PI3K/AKT/mTOR and STAT3 Signaling in Colorectal Cancer Cells.

Polyphyllin II (PPII) is a natural steroidal saponin occurring in Rhizoma Paridis. It has been demonstrated to exhibit anti-cancer activity against a variety of cancer cells. However, the anti-colorectal cancer (CRC) effects and mechanism of action of PPII are rarely reported. In the present study, we showed that PPII inhibited the proliferation of HCT116 and SW620 cells. Moreover, PPII induced G2/M-phase cell cycle arrest and apoptosis, as well as protective autophagy, in CRC cells. We found that PPII-induced autophagy was associated with the inhibition of PI3K/AKT/mTOR signaling. Western blotting results further revealed that PPII lowered the protein levels of phospho-Src (Tyr416), phospho-JAK2 (Tyr1007/1008), phospho-STAT3 (Tyr705), and STAT3-targeted molecules in CRC cells. The overactivation of STAT3 attenuated the cytotoxicity of PPII against HCT116 cells, indicating the involvement of STAT3 inhibition in the anti-CRC effects of PPII. PPII (0.5 mg/kg or 1 mg/kg, i.p. once every 3 days) suppressed HCT116 tumor growth in nude mice. In alignment with the in vitro results, PPII inhibited proliferation, induced apoptosis, and lowered the protein levels of phospho-STAT3, phospho-AKT, and phospho-mTOR in xenografts. These data suggest that PPII could be a potent therapeutic agent for the treatment of CRC.

Association of Prepregnancy Obesity and Remodeled Maternal-Fetal Plasma Fatty Acid Profiles.

Background: Fatty acids, especially polyunsaturated fatty acid (PUFA), are found abundantly in the brain and are fundamental for a fetus's growth. The fatty acid profiles of mothers and fetuses may be affected by maternal prepregnancy body mass index (pre-BMI), thus affecting fetal growth and development. Methods: A total of 103 mother-fetus pairs were divided into overweight/obese (OW, n = 26), normal weight (NW, n = 60), and underweight (UW, n = 17) groups according to pre-BMI. Fatty acid profiles in maternal and umbilical cord plasma were analyzed by gas chromatography. Results: The infant birth BMI z-score of the OW group was higher than that of the NW and UW groups (p < 0.05). The OW mothers had significantly higher plasma n-6 PUFA and n-6/n-3, but lower docosahexaenoic acid (DHA) and n-3 PUFA (p < 0.05). In cord plasma, the proportions of DHA and n-3 PUFA were lower in the OW group (p < 0.05), whereas the n-6/n-3 ratio was higher in the OW group (p < 0.05). The pre-BMI was negatively correlated with cord plasma DHA in all subjects (r = -0.303, p = 0.002), and the same negative correlation can be observed in the OW group (r = -0.561, p = 0.004), but not in the NW and UW groups (p > 0.05). The pre-BMI was positively correlated with cord plasma n-6/n-3 in all subjects (r = 0.325, p = 0.001), and the same positive correlation can be found in the OW group (r = 0.558, p = 0.004), but not in NW and UW groups (p > 0.05). Conclusions: Maternal pre-BMI was associated with the maternal-fetal plasma fatty acid profiles, whereas the adverse fatty acid profiles are more noticeable in the prepregnancy OW mothers.

Boron and Nitrogen-Codoped Carbon Dots as Highly Efficient Electrochemiluminescence Emitters for Ultrasensitive Detection of Hepatitis B Virus DNA.

In this work, boron and nitrogen-codoped carbon dots (BN-CDs) as highly efficient electrochemiluminescence (ECL) emitters with advantages of low excitation potential and high ECL efficiency were prepared to establish a novel ternary ECL system for ultrasensitive detection of HBV-DNA. Especially, both platinum nanoflowers (Pt NFs) and boron radicals (B•) from the BN-CDs could accelerate the reduction of coreactant S2O82- to abundant SO4•- simultaneously, making the BN-CDs have outstanding ECL performance. Impressively, the ECL efficiency of BN-CDs is much higher than that of nondoped CDs and single-doped CDs. In addition, by combining the novel ECL ternary system with the exonuclease III (Exo III)-induced target DNA amplification strategy, an ECL biosensor was constructed to realize the ultrasensitive detection of HBV-DNA from 100 aM to 1 nM, while the limit of detection was 18.08 aM. Therefore, a promising highly efficient ECL emitter was offered to develop a novel ECL detection method for clinical disease analysis.

MicroRNA-23a-5p Is Involved in the Regulation of Lipopolysaccharide-Induced Acute Lung Injury by Targeting HSP20/ASK1.

Inflammation and oxidative stress contribute to the progression of acute lung injury (ALI). MicroRNA-23a-5p (miR-23a-5p) has been reported to regulate inflammation and oxidative stress; however, its role in ALI is still poorly elucidated. Mice were intravenously treated with the miR-23a-5p antagomir, agomir, or the negative controls for 3 consecutive days and then received a single intratracheal injection of lipopolysaccharide (LPS, 5 mg/kg) to induce ALI. Pulmonary function, bronchoalveolar lavage fluids (BALFs), arterial blood gas, and molecular biomarkers associated with inflammation and oxidative stress were analyzed. In addition, murine peritoneal macrophages were isolated and treated with LPS to verify the role of miR-23a-5p in vitro. We detected an elevation of miR-23a-5p expression in the lungs from ALI mice. The miR-23a-5p antagomir was prevented, whereas the miR-23a-5p agomir aggravated inflammation, oxidative stress, lung tissue injury, and pulmonary dysfunction in LPS-treated mice. Besides, the miR-23a-5p antagomir also reduced the productions of proinflammatory cytokines and free radicals in LPS-treated primary macrophages, which were further augmented in cells following the miR-23a-5p agomir treatment. Additional findings demonstrated that the miR-23a-5p agomir exacerbated LPS-induced ALI via activating apoptosis signal-regulating kinase 1 (ASK1), and that pharmacological or genetic inhibition of ASK1 significantly repressed the deleterious effects of the miR-23a-5p agomir. Moreover, we proved that the miR-23a-5p agomir activated ASK1 via directly reducing heat shock protein 20 (HSP20) expression. miR-23a-5p is involved in the regulation of LPS-induced inflammation, oxidative stress, lung tissue injury, and pulmonary dysfunction by targeting HSP20/ASK1, and it is a valuable therapeutic candidate for the treatment of ALI.

Establishment and Characterization of Feline Mammary Tumor Patient-Derived Xenograft Model.

Feline mammary tumor is a relatively commonly diagnosed neoplasm in the cat. Development of new veterinary cancer therapies is limited by the shortage of in vivo models that reproduce tumor microenvironment and metastatic progression. Four feline mammary tumor orthotopic patient-derived xenograft model (PDX) successfully established in NOD-SCID gamma (NSG) mice. The overall success rate of PDX establishment was 36% (4/11). Histological, immunohistochemical, and short tandem repeat analysis showed a remarkable similarity between patient's tumor and xenograft. The tumor grafts conserve original tumor essential features, including distant metastasis. Primary FMT-1807 cell line isolated from FMT-1807PDX tumor tissue. Tumorigenicity of FMT-1807 cells expanded from PDX was assessed by orthotopic injection into NSG mice. Mice yielded tumors which preserve the lung and liver metastasis ability. This work provides a platform for FMT translational investigation.

[The Prognosis and Predictive Value of Complement C3 in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the effect of complement C3 on the prognosis of patients with multiple myeloma (MM), and to establish a predictive model to evaluate the overall survival. METHODS: Eighty newly diagnosed MM patients were enrolled, and clinical characteristics, such as sex, age, platelet count, white blood cell count, ISS stage, FISH, levels of kappa and lammda chain, complement C3 and C4 were retrospectively analyzed. Cox regression model was used for univariate and multivariate analysis about risk factors that affecting the prognosis of the MM patients. A nomogram based on C3 level was established for predicting the prognosis of MM patients. RESULTS: The average age of the MM patients was 63.15±10.41, including 36 males and 44 females. The median overall survival (OS) was 36.3 months, and the median progression-free survival (PFS) was 35.2 months, the 3-year OS rate and PFS rate of the MM patients were 67.5% and 52.5%, respectively. The variants selected by univariate analysis were put into multivariate regression model, the result showed that C3 level ≥0.7 U/L and PLT count <100×109/L were the independent risk factors for OS. Nomogram based on C3 level, PLT count as well as ß2-protein level showed an excellent accuracy in estimating prognosis of MM (C-index: 0.775). CONCLUSION: Patients with C3 level≥0.7 U/L or PLT count <100×109/L show poor prognosis. Nomogram based on the two variants can estimate overall survival of MM patients and provide suggestions to clinical decision.

The composition of bacteria in gut and beebread of stingless bees (Apidae: Meliponini) from tropics Yunnan, China.

Stingless bees are the main pollinators in tropical and subtropical regions. However, there are only a few studies on the structure and composition of bacteria in the gut and beebread of stingless bees, especially in China. To address this shortage of information, we characterized the microbiota of three common species of stingless bees (Lepidotrigona terminata, Lepidotrigona ventralis and Tetragonula pagdeni) and beebread samples of T. pagdeni. The results showed that the gut of stingless bees contained a set of dominant bacteria, including Acetobacter-like, Snodgrassella, Lactobacillus, Psychrobacter, Pseudomonas, Bifidobacterium and other species. The gut microbiota structures of the three stingless bees were different, and the abundances of bacterial species in the gut varied between communities of the same bee species. The reasons for this are manifold and may include food preference, age and genetic differences. In addition, the abundances of Lactobacillus, Carnimonas, Escherichia-Shigella, Acinetobacter and other species were high in the beebread of stingless bees. In conclusion, our findings reveal the bacteria composition and structure of the gut and beebread of stingless bees in China and deepen our understanding of the dominant bacteria of the gut and beebread of stingless bees.

The Succession of the Gut Microbiota in Insects: A Dynamic Alteration of the Gut Microbiota During the Whole Life Cycle of Honey Bees (Apis cerana).

The Asian honey bee Apis cerana is a valuable biological resource insect that plays an important role in the ecological environment and agricultural economy. The composition of the gut microbiota has a great influence on the health and development of the host. However, studies on the insect gut microbiota are rarely reported, especially studies on the dynamic succession of the insect gut microbiota. Therefore, this study used high-throughput sequencing technology to sequence the gut microbiota of A. cerana at different developmental stages (0 days post emergence (0 dpe), 1 dpe, 3 dpe, 7 dpe, 12 dpe, 19 dpe, 25 dpe, 30 dpe, and 35 dpe). The results of this study indicated that the diversity of the gut microbiota varied significantly at different developmental stages (ACE, P = 0.045; Chao1, P = 0.031; Shannon, P = 0.0019; Simpson, P = 0.041). In addition, at the phylum and genus taxonomic levels, the dominant constituents in the gut microbiota changed significantly at different developmental stages. Our results also suggest that environmental exposure in the early stages of development has the greatest impact on the gut microbiota. The results of this study reveal the general rule of gut microbiota succession in the A. cerana life cycle. This study not only deepens our understanding of the colonization pattern of the gut microbiota in workers but also provides more comprehensive information for exploring the colonization of the gut microbiota in insects and other animals.

Brain-Derived Neurotrophic Factor, a New Predictor of Coronary Artery Calcification.

Brain-derived neurotrophic factor (BDNF) plays a functional role in vascular endothelium homeostasis and the alleviation of atherosclerosis. Matrix gla protein (MGP) and Nε-(1-carboxymethyl)-l-lysine (CML) are both confirmed to be VC predictors. This study investigated the association between BDNF, MGP, CML and coronary artery calcification (CAC). Plasma BDNF, MGP, and CML levels were measured in 274 patients who underwent computed tomography to determine the CAC score (Agatston score). It was found that patients with CAC exhibited lower BDNF and MGP and higher CML levels than those without CAC. Plasma BDNF levels in patients with diabetes or hypertension were lower compared with the control groups. In logistic regression analysis, age, hypertension, BDNF, and MGP were independent predictors of CAC. Plasma BDNF and MGP levels were both correlated with the Agatston score even after adjustment for age, total cholesterol level, triglycerides, low-density lipoprotein level, creatinine clearance rate, and the presence of hypertension and diabetes mellitus. In 167 patients with CAC, circulating BDNF level was inversely associated with CML level and positively related to MGP level. In the receiver operating characteristic analysis for CAC, the areas under the curves for BDNF, MGP, and CML were 0.757, 0.777 and 0.653, respectively. In summary, plasma BDNF levels are associated with the Agatston score, and BDNF further predicts the occurrence of CAC.

OIP5-AS1 specifies p53-driven POX transcription regulated by TRPC6 in glioma.

Transcription factors (TFs) control an array of expressed genes. However, the specifics of how a gene is expressed in time and space as controlled by a TF remain largely unknown. Here, in TRPC6-regulated proline oxidase 1 (POX) transcription in human glioma, we report that OIP5-AS1, a long noncoding RNA, determines the specificity of p53-driven POX expression. The OIP5-AS1/p53 complex via its 24 nucleotides binds to the POX promoter and is necessary for POX expression but not for p21 transcription. An O-site in the POX promoter to which OIP5-AS1 binds was identified that is required for OIP5-AS1/p53 binding and POX transcription. Blocking OIP5-AS1 binding to the O-site inhibits POX transcription and promotes glioma development. Thus, the OIP5-AS1/O-site module decides p53-controlled POX expression as regulated by TRPC6 and affects glioma development.