Publications by authors named "Liuli Li"

7 Publications

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Benzo[a]pyrene diol epoxide-induced transformed cells identify the significance of hsa_circ_0051488, a ERCC1-derived circular RNA in pulmonary squamous cell carcinoma.

Mol Carcinog 2021 10 28;60(10):684-701. Epub 2021 Jul 28.

Department of Toxicology, School of Public Health, China Medical University, Shenyang, Liaoning, China.

ERCC1 is a gene for repairing DNA damage whose function is related to carcinogenic-induced tumorigenesis and the effectiveness of platinum therapies. Circular RNAs (circRNAs) are products of posttranscriptional regulation with pleiotropic effects on the pathogenesis of lung cancer. We aim to identify that specific circRNAs derived from ERCC1 can regulate key biological processes involved in the development of lung cancer. We performed bioinformatics analysis, in vitro experiments, and analyzed clinical samples, to determine the biological features of a certain ERCC1-derived circRNA termed as hsa_circ_0051488 in benzo[a]pyrene diol epoxide-induced malignant transformed cell and lung cancer cell. The well-established model of transformed cells provided an ideal platform for analyzing the molecular characteristics of this circRNA in the malignant transformation of lung epithelial cell, which supports that hsa_circ_0051488 functions in the onset and growth of lung squamous cell carcinoma (LUSC). Further analysis indicates that the absence of hsa_circ_0051488 promoted the proliferation of cells with the malignant phenotype. Extensive experiments confirm that hsa_circ_0051488 is present in the cytoplasm and functioned as a competing endogenous RNA. In particular, hsa_circ_0051488 binds to mir-6717-5p, thereby modulating the expression of SATB2 gene, a lung cancer suppressor. Furthermore, our in silico experiments indicate that SATB2 can inhibit multiple tumor pathways and its expression positively correlated with the tumor suppressor gene CRMP1. These findings suggest a possible regulatory mechanism of hsa_circ_0051488 in LUSC, and that the newly discovered hsa_circ_0051488/miR-6717-5p/SATB2 axis may be a potential route for therapeutic intervention of LUSC.
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http://dx.doi.org/10.1002/mc.23335DOI Listing
October 2021

Co-exposure to BPA and DEHP enhances susceptibility of mammary tumors via up-regulating Esr1/HDAC6 pathway in female rats.

Ecotoxicol Environ Saf 2021 Sep 26;221:112453. Epub 2021 Jun 26.

Department of Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New District, Shenyang 110122, Liaoning Province, PR China. Electronic address:

Breast cancer (BrCa) as one of the major malignancies threatening women's health worldwide occurs due to the genetic and environmental interactions. Epidemiological studies have suggested that exposure to endocrine disrupting chemicals (EDCs) can elevate the risk of breast cancer. Di-(2-ethylhexyl)-phthalate (DEHP) and bisphenol A (BPA) are known as two typical EDCs. Although several studies have implied that there appear to have adverse effects of exposure to BPA or DEHP alone on breast development, no study to date has demonstrated the exact toxic effect of combined exposure to DEHP and BPA on breast tumorigenesis. In the present study, we performed an in vivo experiment including 160 female Sprague-Dawley (SD) rats, in which 80 rats were randomly allocated to 4 groups including control group given to normal diet, DEHP (150 mg/kg body weight/day), BPA (20 mg/kg body weight/day), and DEHP (150 mg/kg body weight/day) combined with BPA (20 mg/kg body weight/day) by gavage for 30 weeks. Additionally, a DEN/MNU/DHPN (DMD)-induced carcinogenesis animal model was also established to assess their effect on tumor promotion. Namely, the other 80 SD rats were separated into another 4 groups: in addition to DMD initiation each group treated with vehicle, DEHP, BPA and the combination of BPA and DEHP respectively. Our data demonstrated that BPA alone or in combination with DEHP may induce hyperplasia of mammary glands, including the proliferation of ductal epithelial cells and an increase in the number of lobules and acinus after a 30-week exposure. Notably, co-exposure to DEHP and BPA increased the incidence and reduced the latency of mammary tumor, which seemed to enhance the susceptibility of carcinogens-induced tumor. Mechanistically, our results supported the hypothesis that exposure to BPA and DEHP might promote breast cancer dependent on Esr1 and HDAC6 as pivotal factors, and further lead to the activation of oncogene c-Myc. Our study suggested that BPA combined with DEHP facilitate the occurrence of mammary tumors, which contributed to advance our understanding in the complex effects of compound exposure to endocrine disrupting chemicals.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112453DOI Listing
September 2021

Bisphenol A at a human exposed level can promote epithelial-mesenchymal transition in papillary thyroid carcinoma harbouring BRAF mutation.

J Cell Mol Med 2021 02 19;25(3):1739-1749. Epub 2021 Jan 19.

Department of Toxicology, School of Public health, China Medical University, Shenyang, China.

Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, alters the function of endocrine system and enhances the susceptibility to tumorigenesis in several hormone-dependent tumours as thyroid carcinoma. About 50% of papillary thyroid cancers (PTC), the most common type of thyroid malignancy, harbours the BRAF mutation. This study aimed to investigate a potential combined effect of BPA exposure and BRAF mutation on epithelial-mesenchymal transition (EMT) in PTC. Firstly, the level of BPA in plasma, the evaluation of BRAF mutation and the level of EMT-related proteins in PTC samples were individually determined. Additionally, the migration, invasion, colony formation capacity and the expression of EMT-related proteins after exposure to BPA were precisely analysed in vitro thyroid cells genetically modified by the introduction of BRAF mutation. Moreover, ERK-Cox2 signalling pathway was also introduced to explore the possible mechanism in PTC development. As expected, whether the clinical investigation or cultured thyroid cells demonstrated that BPA at a concentration compatible with human exposed levels (10  M) synergized with the BRAF mutation promoted EMT via the activation of ERK-Cox2 signalling pathway. Our findings offer some evidence that BPA as an environmental risk factor can facilitate the progression of PTC harbouring BRAF mutation.
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http://dx.doi.org/10.1111/jcmm.16279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875916PMC
February 2021

The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway.

J Clin Lab Anal 2021 Mar 12;35(3):e23655. Epub 2020 Dec 12.

Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Department of Surgical Oncology and General Surgery, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: N6-methyladenosine (m6A) modification may participate in the regulation of occurrence and development of tumors. However, the m6A level and the potential regulatory mechanism of m6A in gastric cancer (GC) remain uncertain.

Methods: RNA m6A quantification assay was conducted to detect the m6A level in GC tissues and cell lines. Methyltransferase-like 14 (METTL14) expression in GC tissues was explored by bioinformatics and immunohistochemistry. Then, the function of METTL14 in GC cells was examined by CCK-8, colony formation assay, wound healing assay, and Transwell assay. Besides, Western blotting was conducted to probe the PI3K/AKT/mTOR pathway and the epithelial-mesenchymal transformation (EMT) pathway-related gene expression.

Results: The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 was downregulated in GC by analyzing both clinical samples and bioinformatics. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3K/AKT/mTOR pathway and the EMT pathway, respectively.

Conclusions: Our findings indicate that METTL14 partakes in the biological process of GC as a tumor suppressor and may be an emerging biomarker in GC.
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http://dx.doi.org/10.1002/jcla.23655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957981PMC
March 2021

Combined effects of di (2-ethylhexyl) phthalate and bisphenol A on thyroid hormone homeostasis in adolescent female rats.

Environ Sci Pollut Res Int 2020 Nov 17;27(32):40882-40892. Epub 2020 Jul 17.

Department of Toxicology, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China.

Phthalates and bisphenols are two typical classes of endocrine-disrupting chemicals (EDCs) which cause endocrine disorder in humans and animals. Phthalates and bisphenols are suggested to be associated with thyroid dysfunction. However, the effects of combined exposure and the detailed mechanisms are yet poorly understood. We investigated the combined effects of di (2-ethylhexyl) phthalate (DEHP) and bisphenol A (BPA) on thyroid function during puberty. Female Sprague Dawley rats were gavaged from postnatal 28 to 70 days with a single or combined exposure of DEHP (0, 150, and 750 mg/kg/day) and BPA (0, 20, and 100 mg/kg/day) according to a 3 × 3 factorial design. The thyroid weights reduced after combined exposure to the highest dose of DEHP and BPA, which noted their adverse effects on thyroid. Additionally, DEHP could increase the number of follicular epithelial cells in thyroid. Both DEHP and in combination with BPA could disturb the levels of thyroid hormones in serum, such as TT3 and TT4. Meanwhile, the possible mechanism was also discussed in the present study. DEHP treatment induced a significant increase of phosphorylation of cAMP-response element binding protein (Creb) via estrogen receptor α (Esr1), while the upregulation was nullified by the concomitant presence of BPA. In conclusion, the complex action of DEHP/BPA mixture may disturb the thyroid hormone homeostasis, which ultimately would affect the development of thyroid during puberty.
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http://dx.doi.org/10.1007/s11356-020-09949-wDOI Listing
November 2020

AC138128.1 an Intronic lncRNA originating from ERCC1 Implies a Potential Application in Lung Cancer Treatment.

J Cancer 2019 9;10(16):3608-3617. Epub 2019 Jun 9.

Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, P.R. China.

Lung cancer is one of the most devastating tumors with a high incidence and mortality worldwide. Polymorphisms and expression of commonly predicted the occurrence and prognosis of lung cancer. However, few studies have focused on long non-coding RNAs related to though some studies reminded the importance of its post-transcriptional regulation. In the present study, an intronic lncRNA AC138128.1 originated from was firstly identified in microarray chip and database, and its possibility as a novel biomarker to predict lung cancer treatment was further discussed. Firstly, the qRT-PCR data showed that AC138128.1 expression was much lower in lung cancer comparing with its para-cancer tissues, which further analyzed by ROC curve. Similarly, the difference was also verified in 16HBE, A549 and LK cells. Then AC138128.1 expression was found to have an increasing trend in a dose or time-dependent manner after cisplatin treatment. Finally, the subcellular distribution of AC138128.1 reminded that AC138128.1 was mainly expressed in the nucleus. Interestingly a positive relationship between AC138128.1 and expression was only found in cancer tissues, which reminded AC138128.1 may be involved in the regulation of ERCC1. Therefore, as a preliminary exploration of the lncRNA originated from , the present study suggested AC138128.1 is of potential value in predicting platinum analogue benefit in lung cancer.
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http://dx.doi.org/10.7150/jca.31832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636308PMC
June 2019

An Antagonism Joint Action of Lead and Di-2-Ethylhexyl Phthalate Explains an Improved Ability of Learning and Memory after Combined Exposure in Weaning Rats.

Biol Trace Elem Res 2019 Sep 6;191(1):126-134. Epub 2018 Dec 6.

Department of Toxicology, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China.

Lead and di-2-ethylhexyl phthalate (DEHP) are widely distributed in the environment, and their neurotoxicity has caused a widespread concern. The complexity of environmental exposure provides the possibility of their combined exposure. The present study aims to describe a joint neurotoxicity and clarify the potential mechanism after combined exposure to lead and DEHP. A 2 × 3 factorial design was used to analyze either single effects or their interaction by a subchronic lead and DEHP exposure model of the male weaning rats. Similar to the previous study, lead or DEHP single exposure showed an increased neurotoxicity. Interestingly, our neurobehavioral test showed the rats in the combined exposure groups had a better ability of learning and memory compared with the single-exposure ones. It seemed to reflect an antagonism joint action in neurotoxicity after combined exposure. The content of dehydroepiandrosterone (DHEA) in serum and the mRNA level of brain-derived neurotrophic factor (Bdnf) in the hippocampus showed a similar trend to the ability of learning and memory. However, there was insufficient evidence to support the joint action on some indexes of oxidative stress such as malondialdehyde (MDA), the ratio of reduced glutathione(GSH) to oxidized glutathione(GSSG), γglutamylcysteine synthetase (γ-GCS), glutathione-s transferase (GST), and nuclear factor E2-related factor 2 (Nrf2) mRNA expression in the hippocampus. In a word, our current study reminded a unique antagonism joint action of neurotoxicity after combined exposure to lead and DEHP, which may contribute to understanding some shallow mechanism of the joint toxicity due to the complexity of environmental pollutant exposure.
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http://dx.doi.org/10.1007/s12011-018-1586-5DOI Listing
September 2019
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