Cancers
·
2023
·Vol. 15
·期 6
·1724
·
IF 5.2
Khalil Ur Rahman,Shuo Yang,Nasir Azam,Zhen Yuan,Jiawen Yu,Chunhui Zhao,Bin Feng
Simple SummaryBreast cancer is a disease that begins in the cells of the breast. Although it is most common in women, it can also occur in men, though this is rare. Early detection and treatment are crucial to improving outcomes and survival rates. Risk factors include age, family history, certain gene mutations, prior history of breast cancer, exposure to estrogen, and lifestyle habits like alcohol consumption and inactivity. Symptoms include changes in the skin on the breast, such as dimpling, lumps or thickening, changes in size or shape, and discharge from the nipple. Diagnosis is often made through a clinical breast exam, mammogram, biopsy, and possibly additional imaging tests. Treatment options include surgery, chemotherapy, radiation therapy, hormone therapy, and targeted therapy. The choice of treatment method depends on the stage and characteristics of cancer.AbstractBreast cancer is considered the solid tumor most sensitive to chemotherapy. However, it can become resistant to various chemotherapeutic drugs, including doxorubicin, which triggers cell death by intercalation between DNA bases, free radical formation, and topoisomerase II inhibition. When drug resistance develops, several miRNAs are dysregulated, suggesting that miRNAs may play a significant role in resistance formation. In the current study, we investigated how doxorubicin sensitivity of breast cancer cells is affected by miR-153-3p and its target gene. The MTT method was used to determine the chemo-sensitizing effect of miR-153-3p on doxorubicin in MCF-7 and MDA-MB-231 cell lines. Results of Western blot and dual luciferase confirmed that miR-153-3p targets KIF20A and decreases its expression. Transwell and flow cytometry experiments showed that miR-153-3p and doxorubicin together had higher effects on MCF-7 and MDA-MB-231 cell proliferation, migration, and invasion, as well as increasing apoptosis and arresting cells in the G1 phase. Proteins related to apoptosis and the cell cycle exhibited the same tendency. Intracellular vesicle formation was inhibited and RAB26 was also downregulated by treatment with miR-153-3p alone or in combination with doxorubicin. Doxorubicin’s ability to suppress tumors may be enhanced by miR-153-3p, according to in vivo studies. According to our findings, miR-153-3p has a direct effect on KIF20A and may regulate the formation of intracellular vesicles, which in turn makes breast cancer cells more susceptible to doxorubicin.Keywords:miR-153-3p;chemosensitivity;breast cancer;doxorubicin;KIF20A
研究领域:
肿瘤学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2022
·
IF 3.322
Weimin Lin,Xianyu Wen,Xuexin Li,Lei Chen,Wei Wei,Lifan Zhang,Jie Chen
CeRNA effect was an important regulation mode of miRNA mediated bio-activities, however, most of the researches of ceRNA were on ncRNAs synergetic with mRNAs, the exploration of ceRNA effect regulated mRNA interaction was still lack of. Besides, C/EBPα was one of the most crucial adipogenic regulators, which has been demonstrated to form a protein complex with FOXO1 to mediate AdipoQ expression. So that, we try to explore whether the ceRNA effect mediated the interaction of C/EBPα and FOXO1, and identified the key miRNAs of their ceRNA effect. In this paper, we found the ceRNA effect of C/EBPα and FOXO1 mediated their protein complex formation, furthermore regulated its transcriptional role for AdipoQ , thereby influencing pre-adipocytes adipogenesis . More importantly, we demonstrated that the miR-144 was the decisive factor that mediated the ceRNA effect of C/EBPα and FOXO1 to influence AdipoQ , thus regulated pre-adipocytes adipogenesis. This research will provide a new supplementary idea of the miRNA role in mediating coding RNA interaction that regulates pre-adipocyte adipogenesis.
研究领域:
分子生物学
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细胞生物学
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基因组学
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DOI
PubMed
高影响因子
GENOMICS
·
2021
·
IF 5.736
Shiliang Dong,Minrui Ma,Ming Li,Yuexin Guo,Xiaoxiao Zuo,Xiaobin Gu,Mingzhi Zhang,Yonggang Shi
Maternally expressed 3 (MEG3) and RNA binding motif single stranded interacting protein 3 (RBMS3) are abnormally expressed in breast cancer susceptibility genes (BRCA), but the mechanism of the two in breast cancer (BC) is unclear. By performing in vivo and in vitro experiments, we found that MEG3 and RBMS3 were low-expressed, negatively correlated with high-expressed miR-141-3p, were positively correlated with each other in BC. MEG3 targeted miR-141-3p, and miR-141-3p targeted RBMS3. MEG3, which was mainly distributed in BC cytoplasm, could down-regulate miR-141-3p and up-regulate RBMS3, and reverse effect of miR-141-3p on related gene expressions and on promoting cancer development. Overexpressed MEG3 inhibited growth of xenografts, promoted cell apoptosis via regulating apoptosis related factors, and up-regulated RBMS3 expression but down-regulated miR-141-3p. The findings of this study showed that MEG3 inhibited proliferation and promoted apoptosis of BC cells through the miR-141-3p/RBMS3 axis, and MEG3 inhibited growth of xenografts through miR-141-3p.
研究领域:
肿瘤学
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分子生物学
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癌症遗传学
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DOI
PubMed
高影响因子
Molecular & Cellular Toxicology
·
2022
·
IF 1.718
Li Hua,Guo Junyu,Qin Zhongwei,Wei Mingwei,Guo Houji,Huang Fuda
Background Emerging evidence has indicated that circular RNAs (circRNAs) play vital roles in colorectal cancer (CRC). CircRNA leucine zipper and EF-hand containing transmembrane protein 1 (circLETM1) have been found to be ectopic in CRC, but their role in CRC has not been studied yet. Objective This study aims to explore the roles of circLETM1 in CRC and the possible molecular mechanism. Result The results showed that circLETM1 was highly expressed in CRC cells, and was localized at the cytoplasm. Functional assays verified that overexpression of circLETM1 could facilitate, but circLETM1 downregulation could hamper proliferation, migration and invasion abilities of CRC cells. In addition, mechanism assays found that circLETM1 absorbed and reduced microRNA (miR)-143-3p expression to promote keratin 80 (KRT80). Rescue experiments proved that circLETM1 mediated CRC proliferation, migration and invasion through KRT80. Conclusion Taken together, our results suggested that circLETM1 promotes proliferation, migration and invasion through the miR-143-3p/KRT80 axis in CRC. Therefore, targeting circLETM1 may provide a novel option for CRC treatment.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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DOI
高影响因子
JOURNAL OF CLINICAL LABORATORY ANALYSIS
·
2022
·Vol. 36
·期 11
·e24698
·
IF 3.124
Chunfa Chen,Liang Liu
Background Osteosarcoma (OS) is a highly recurrent malignancy occurring among adolescents. The goal of this research was to scrutinize the role and action mechanism of KLF3-AS1 in OS. Methods Western blotting and quantitative reverse transcription real-time PCR were conducted to ascertain the mRNA expressions of miR-338-3p, KLF3-AS1, and MEF2C in OS cell lines and tissue samples. Colony formation and CCK-8 experiments were done to evaluate the proliferative capacity of the cells. Western blotting was also executed to measure the relative expressions of the proteins Bcl-2 and Bax. RNA immunoprecipitation and dual luciferase reporter experiments were carried out to validate the target relationships among MEF2C, KLF3-AS1, and miR-338-3p. Mouse xenograft models were created to assess the influences of KLF3-AS1 on the growth of tumors in vivo. Results Elevated levels of KLF3-AS1 and MEF2C and reduced amounts of miR-338-3p were identified in OS. KLF3-AS1 targeted miR-338-3p, and miR-338-3p further targeted MEF2C. Silencing KLF3-AS1 induced apoptosis and attenuated proliferation in vitro and repressed the tumor growth in vivo. Inhibiting miR-338-3p inverted the cancer-suppressing effects of KLF3-AS1 silencing. Meanwhile, loss of MEF2C partially eliminated the effects brought about by miR-338-3p downregulation, namely the stimulation of cell growth and suppression of apoptosis. Conclusions Silencing of KLF3-AS1 could repress the growth of cells and induce apoptosis by regulating miR-338-3p/MEF2C in OS. This suggests that the regulatory axis KLF3-AS1/miR-338-3p/MEF2C is a prospective target for OS treatment.
研究领域:
肿瘤学
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分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
CANCER BIOLOGY & THERAPY
·
2020
·
IF 3.659
Chunhua Zhou,Wencheng Kong,Tongfa Ju,Qi Xie,Lulu Zhai
Background Studies showed that microRNAs (miRNAs) are important regulators in drug resistance. The current study investigated the role of miR-185-3p and its predicted target gene AQP5 in 5-FU-insensitive colorectal cancer (CRC) cells.Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and Spearman’s correlation analysis were conducted to determine the correlation of expression levels of miR-185-3p and AQP5 from CRC tissues. HCT-116 and HCT-8 cells were treated by gradient concentration of 5-FU to construct 5-FU-resistant CRC model. The inhibition and viability of 5-FU-resistant cells were detected by MTT assay, and cell migration and invasion ability were determined by wound healing and transwell assay. The expressions of miR-185-3p and AQP5 were measured by qRT-PCR. StarBase and dual-luciferase reporter assay were used to predict and confirm the interaction between miR-185-3p and AQP5. Further experiments were performed to explore the function of miR-185-3p in 5-FU-resistant cells through regulating aquaporin-5 (AQP5). The levels of EMT-associated markers and AQP5 were determined by conducting Western Blot and qRT-PCR.Results We found that 5-FU-resistant CRC cells showed a lower inhibition rate, and higher migration and invasion abilities. MiR-185-3p was low-expressed in CRC tissues and 5-FU-resistance cells, and it targeted and regulated the expression of AQP5, which was found up-regulated in CRC and 5-FU-resistance CRC cells (r = −0.29, P < .05). Furthermore, miR-185-3p mimic enhanced the chemo-sensitivity of 5-FU-resistant cells, while overexpressed AQP5 reversed such an effect produced by miR-185-3p mimic.Conclusion MiR-185-3p mimic enhances the chemosensitivity of CRC cells via AQP5. Our research provides a potential therapeutic target for 5-FU-resistant CRC cells.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2020
·Vol. 22
·期 5
·3944-3954
·
IF 2.1
Li Zhu,Xueying Zhou,Shanshan Li,Jianmeng Liu,Jingyan Yang,Xiangyun Fan,Shengnian Zhou
Cerebral ischemia is a common cerebrovascular disease caused by the occlusion of a cerebral blood vessel. MicroRNAs (miRNAs/miRs) are emerging regulators of various human diseases, including cerebral ischemia. Upregulation of miR‑183‑5p has been reported to alleviate liver injury induced by ischemia‑reperfusion (I/R). However, the effect of miR‑183‑5p on cerebral ischemia injury remains unknown. The present study evaluated the effects of miR‑183‑5p on ischemia injury using ischemic models of mouse brains exposed to transient middle cerebral artery occlusion and Neuro‑2A (N2A) neuroblastoma cells exposed to oxygen‑glucose‑deprivation (OGD) and subsequently reoxygenated. Ischemia was evaluated in mice using neurological function scores, cerebral edema, 2,3,5‑triphenyltetrazoliumchloride, Nissl and Fluoro‑Jade B staining assays. In addition, miR‑183‑5p expression, N2A cell viability and the expression levels of apoptosis‑associated proteins were detected by quantitative PCR, Cell Counting Kit‑8 assay, flow cytometry and western blotting. The association between miR‑183‑5p and phosphatase and tensin homolog (PTEN) was also confirmed by a luciferase reporter assay. The results revealed that miR‑183‑5p expression was decreased and brain damage was increased in ischemic mice compared with the sham group. Additionally, miR‑183‑5p levels were reduced, and apoptosis was increased in N2A cells exposed to ischemia compared with the control group. Following transfection with agomiR‑183‑5p, cerebral ischemic injury and apoptosis levels were reduced in the in vivo I/R stroke model and OGD‑induced N2A cells. In addition, PTEN was determined to be a target of miR‑183‑5p following elucidation of a direct binding site. Overexpression of PTEN reversed the miR‑183‑5p‑induced N2A cell apoptosis inhibition and survival after OGD. The results of the present study suggested that miR‑183‑5p reduced ischemic injury by negatively regulating PTEN, which may aid the development of a novel therapeutic strategy for cerebral ischemia.
研究领域:
神经科学
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分子生物学
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医学研究
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DOI
PubMed
高影响因子
METABOLIC BRAIN DISEASE
·
2022
·Vol. 38
·期 1
·233-244
·
IF 3.655
Xiao Gaopeng,Yu Liuqiong,Tan Wenmin,Yang Hao,Li Wensen,Xia Rongzhou,Li Yujin
Propofol has a tumor-suppressive role in glioma, but the mechanism by which propofol is involved in glioma progression is largely unknown. This study aims to explore a potential circular RNAs (circRNAs)/microRNAs (miRNAs)/mRNA network in response to Propofol in glioma. Human glioma cell lines (U251 and LN229) were suffered from Propofol treatment (5 μg/mL for 24 h) and transfection. circRNA mitogen-activated protein kinase 4 (circMAPK4), miR-622, homeobox A9 (HOXA9) abundances were determined by quantitative reverse transcription polymerase chain reaction and western blot. Migration and invasion were analyzed via transwell analysis. Cell proliferation was evaluated using Cell Counting Kit-8 and colony formation analysis. Cell apoptosis and related protein expression were determined via flow cytometry and western blot. Target relationship was assessed via dual-luciferase reporter analysis, RNA pull-down and RNA immunoprecipitation. Propofol reduced circMAPK4 expression. Propofol inhibited cell proliferation, migration and invasion, while increased apoptosis via decreasing circMAPK4 in glioma cells. miR-622 was targeted via circMAPK4. circMAPK4 knockdown decreased glioma cell growth, migration and invasion by up-regulating miR-622. miR-622 knockdown reversed the effect of Propofol on glioma progression. HOXA9 was targeted by miR-622, and its expression was decreased by Propofol treatment. miR-622 overexpression restrained glioma progression via decreasing HOXA9. Propofol regulated circMAPK4/miR-622/HOXA9 axis in glioma cells. Propofol constrains glioma progression by regulating circMAPK4/miR-622/HOXA9 axis in vitro. Propofol restrains glioma cell growth, migration and invasion. circMAPK4 can regulate HOXA9 by sponging miR-622 in glioma cells. Propofol represses glioma progression via a circMAPK4/miR-622/HOXA9 axis.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2021
·
IF 8.071
Rili Hao,Xinyu Song,Dongxiao Sun-Waterhouse,Xintong Tan,Feng Li,Dapeng Li
Cadmium (Cd), as an environmental pollutant, can lead to nephrotoxicity. However, its nephrotoxicological mechanisms have not been fully elucidated. In this study, Cd (1.5 mg/kg body weight, gavaged for 4 weeks) was found to induce the renal damage in mice, based on indicators including Cd concentration, kidney index, serum creatinine and blood urea nitrogen levels, pro-inflammatory cytokines and their mRNA expressions, levels of Bcl-2, Bax and caspase9, and histopathological changes of the kidneys. Furthermore, Cd-caused detrimental changes through inducing inflammation and apoptosis via the miR-34a/Sirt1/p53 axis. This is the first report on the role of miR-34a/Sirt1/p53 axis in regulating Cd-caused apoptosis and nephrotoxicity in mice. The findings obtained in this study provide new insights into miRNA-based regulation of heavy metal induced-nephrotoxicity.
研究领域:
毒理学
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分子生物学
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DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2025
·Vol. 2025
·期 1
·4955849
·
IF 4.2
Zhengrong Chen,Dingwei Yan,Suyu Guo,Yiyi Song,Xinxing Zhang,Wenjing Gu,Heting Dong,Li Huang
Background: This study aimed to explore the mechanisms underlying T-cell differentiation in asthma. Methods and Results: Flow cytometry was performed to detect Th cells. LC-MS/MS was performed to assess lipid metabolism. HE staining was performed to assess the pathological changes of the lung tissues. ELISA was performed to detect cytokine levels. The results of quantitative real-time polymerase chain reaction (qRT-PCR) and western blot showed that miR-192-5p expression was decreased, while SCD1 expression was increased in CD4 + T cells isolated from the peripheral blood of children with asthma. The dual luciferase reporter assay determined the direct interaction between miR-192-5p and SCD1. MiR-192-5p inhibitor reduced ASCL3 and PPARα, increased FASN and SREBP1c mRNA expression and protein levels in mouse spleen CD4 + T cells, and elevated Th2 and Th17 cells, but these effects were reversed by the SCD1 inhibitor. Oleic acid (OA) reduced Th1 cells and increased Th2 and Th17 cells in mouse spleen CD4 + T cells treated with an SCD1 inhibitor. Additionally, pri-miR-192-5p expression was increased in CD4 + T cells isolated from the peripheral blood of asthmatic children, and the deletion of METTL3 upregulated pri-miR-192-5p expression in an m6A-dependent manner. MiR-192-5p mimic and inhibitor both reversed miR-192-5p and SCD1 expression affected by overexpression or deletion of METTL3, both in vivo and in vitro . Furthermore, METTL3 overexpression attenuated lung inflammation, elevated Th1 cells, and reduced Th2 and Th17 cells in CD4 + T cells isolated from the peripheral blood of asthmatic mice. These effects were reversed by the miR-192-5p inhibitor. Conclusion: These results suggest that METTL3/miR-192-5p/SCD1 axis regulates lipid metabolism and affects T cell differentiation, thus affecting asthma progression. This study may provide novel insights into the pathogenesis of asthma and a new treatment strategy.
研究领域:
免疫学
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分子生物学
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呼吸病学
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产品关联
DOI
PubMed
高影响因子
Translational Oncology
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2021
·
IF 4.243
Qiuli Wang,Dong Liang,Peng Shen,Yang Yu,Yuan Yan,Wei You
Previous study has confirmed that hsa_circ_0092276 is highly expressed in doxorubicin (DOX)-resistant breast cancer cells, indicating that hsa_circ_0092276 may be involved in regulating the chemotherapy resistance of breast cancer. Here we attempted to investigate the biological role of hsa_circ_0092276 in breast cancer. We first constructed DOX-resistant breast cancer cells (MCF-7/DOX and MDA-MB-468/DOX). The 50% inhibiting concentration of MCF-7/DOX and MDA-MB-468/DOX cells was significantly higher than that of their parental breast cancer cells, MCF-7 and MDA-MB-46. MCF-7/DOX and MDA-MB-468/DOX cells also exhibited an up-regulation of drug resistance-related protein MDR1. Compared with MCF-7 and MDA-MB-46 cells, hsa_circ_0092276 was highly expressed in MCF-7/DOX and MDA-MB-468/DOX cells. Hsa_circ_0092276 overexpression enhanced proliferation and the expression of LC3-II/LC3-I and Beclin-1, and repressed apoptosis of breast cancer cells. The effect of hsa_circ_0092276 up-regulation on breast cancer cells was abolished by 3-methyladenine (autophagy inhibitor). Hsa_circ_0092276 modulated autophagy-related gene 7 (ATG7) expression via sponging miR-384. Hsa_circ_0092276 up-regulation promoted autophagy and proliferation, and repressed apoptosis of breast cancer cells, which was abolished by miR-384 overexpression or ATG7 knockdown. In addition, LV-circ_0092276 transfected MCF-7 cell transplantation promoted autophagy and tumor growth of breast cancer in mice. In conclusion, our data demonstrate that hsa_circ_0092276 promotes autophagy and DOX resistance in breast cancer by regulating miR-348/ATG7 axis. Thus, this article highlights a novel competing endogenous RNA circuitry involved in DOX resistance in breast cancer.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ONCOLOGY REPORTS
·
2025
·Vol. 53
·期 5
·1-14
·
IF 3.9
Ying Hu,Xin Liu,Ziheng Yuan,Jianping He,Run Ma,Yuming Wang,Genfa Yi
Globally, lung adenocarcinoma (LUAD) remains the leading cause of cancer‑related mortality, highlighting the urgent need for innovative therapeutic approaches. Necroptosis has been recognized as a crucial mechanism for inhibiting cancer progression. Research has revealed a significant association between microRNA (miRNA)‑mediated necroptosis and tumor progression. The present study aimed to elucidate the role and underlying mechanisms of miR‑10b‑5p in regulating necroptosis in the context of LUAD. In an investigation of LUAD, miRNA sequencing was conducted on both LUAD and adjacent non‑tumor tissues, followed by the integration of external database information to identify specific target miRNAs. The expression of miR‑10b‑5p was verified in LUAD tissues and corresponding adjacent non‑cancerous tissues using immunohistochemistry. In vitro experiments, utilizing LUAD cell lines engineered to modulate miR‑10b‑5p levels, assessed its effects on cellular activities and necroptosis. The inhibition of PKP3 by miR‑10b‑5p was determined using a dual luciferase reporter system. Furthermore, alterations in miR‑10b‑5p levels were found to affect PKP3 expression and inhibit the RIPK3/MLKL signaling pathway, as evidenced by western blot analysis in LUAD cell lines. The effect of PKP3 knockdown on cell activity and necroptosis in LUAD cell lines with low miR‑10b‑5p expression levels was assessed using cell function assays. Finally, a nude mouse xenograft model was used to investigate the effect of miR‑10b‑5p on LUAD growth in vivo and its specific mechanism of action. It has been revealed that miR‑10b‑5p levels are significantly elevated in LUAD specimens. Further investigations demonstrated that an increase in miR‑10b‑5p enhances the proliferation of LUAD cells and suppresses the progression of necroptosis, as evidenced by in vitro experiments. Through dual luciferase reporter assays, PKP3 was confirmed as a direct target negatively regulated by miR‑10b‑5p, leading to reduced expression levels. Western blot analysis indicated that miR‑10b‑5p inhibits the RIPK3/MLKL pathway activation through downregulation of PKP3, which leads to increased cell proliferation and decreased necroptosis. However, knockdown of PKP3 reversed the inhibitory effect of miR‑10b‑5p inhibitors on cellular activity and inhibited necrosis by suppressing the RIPK3/MLKL signalling pathway. In addition, animal model studies demonstrated that inhibition of miR‑10b‑5p activated the RIPK3/MLKL pathway by promoting PKP3 expression and significantly reduced LUAD growth by promoting necroptosis. In conclusion, our studies have revealed that the miR‑10b‑5p functions as a tumorigenic factor, enhancing various cellular activities in LUAD cells and suppressing necroptosis by specifically targeting PKP3, thereby inhibiting activation of the RIPK3/MLKL pathway. Importantly, interventions using inhibitors that specifically target miR‑10b‑5p have shown significant success in impeding the progression of LUAD by promoting necroptosis in both cellular and animal models. Thus, targeting miR‑10b‑5p holds considerable potential as a therapeutic strategy for LUAD.
研究领域:
肿瘤学
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分子生物学
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医学遗传学
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产品关联
DOI
PubMed
高影响因子
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