The prognostic miR-532-5p-correlated ceRNA-mediated lipid droplet accumulation drives nodal metastasis of cervical cancer
Introduction: The prognosis for cervical cancer (CC) patients with lymph node metastasis (LNM) is extremely poor. Lipid droplets (LDs) have a pivotal role in promoting tumor metastasis. The crosstalk mechanism between LDs and LNM modulated in CC remains largely unknown. Objectives: This study aimed...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123221001909 |
| _version_ | 1818138384829251584 |
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| author | Chunliang Shang Yuan Li Tianhui He Yuandong Liao Qiqiao Du Pan Wang Jie Qiao Hongyan Guo |
| author_facet | Chunliang Shang Yuan Li Tianhui He Yuandong Liao Qiqiao Du Pan Wang Jie Qiao Hongyan Guo |
| author_sort | Chunliang Shang |
| collection | DOAJ |
| description | Introduction: The prognosis for cervical cancer (CC) patients with lymph node metastasis (LNM) is extremely poor. Lipid droplets (LDs) have a pivotal role in promoting tumor metastasis. The crosstalk mechanism between LDs and LNM modulated in CC remains largely unknown. Objectives: This study aimed to construct a miRNA-dependent progonostic model for CC patients and investigate whether miR-532-5p has a biological impact on LNM by regualting LDs accumulation. Methods: LASSO-Cox regression was applied to establish a prognostic prediction model. miR-532-5p had the lowest P-value in RNA expression (P < 0.001) and prognostic prediction (P < 0.0001) and was selected for further study. The functional role of the prognostic miR-532-5p-correlated competing endogenous RNA (ceRNA) network was investigated to clarify the crosstalk between LDs and LNM. The underlying mechanism was determined using site-directed mutagenesis, dual luciferase reporter assays, RNA immunoprecipitation assays, and rescue experiments. A xenograft LNM model was established to evaluate the effect of miR-532-5p and orlistat combination therapy on tumor growth and LNM. Results: A novel 5-miRNAs prognostic signature was constructed to better predict the prognosis of CC patient. Further study demonstrated that miR-532-5p inhibited epithelial-mesenchymal transition and lymphangiogenesis by regulating LDs accumulation. Interestingly, we also found that LDs accumulation promoted cell metastasis in vitro. Mechanistically, we demonstrated a miR-532-5p-correlated ceRNA network in which LINC01410 was bound directly to miR-532-5p and effectively functioned as miR-532-5p sponge to disinhibit its target gene-fatty acid synthase (FASN). Combined therapy with miR-532-5p and FASN inhibitor-orlistat further inhibited tumor growth and LNM in vivo. Conclusion: Our findings highlight a LD accumulation-dependent mechanism of miR-532-5p-modulated LNM and support treatment with miR-532-5p/orlistat as novel strategy for treating patients with LNM in CC. |
| first_indexed | 2024-12-11T10:11:21Z |
| format | Article |
| id | doaj.art-a47318073f3943c095f41cbeedf8db99 |
| institution | Directory Open Access Journal |
| issn | 2090-1232 |
| language | English |
| last_indexed | 2024-12-11T10:11:21Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj.art-a47318073f3943c095f41cbeedf8db992022-12-22T01:11:44ZengElsevierJournal of Advanced Research2090-12322022-03-0137169184The prognostic miR-532-5p-correlated ceRNA-mediated lipid droplet accumulation drives nodal metastasis of cervical cancerChunliang Shang0Yuan Li1Tianhui He2Yuandong Liao3Qiqiao Du4Pan Wang5Jie Qiao6Hongyan Guo7Department of Obstetrics and Gynecology, Peking University Third Hospital, 100191 Beijing, ChinaDepartment of Obstetrics and Gynecology, Peking University Third Hospital, 100191 Beijing, ChinaDepartment of Obstetrics and Gynecology, Peking University Third Hospital, 100191 Beijing, ChinaDepartment of Obstetrics and Gynecology, The First Affliated Hospital, Sun Yat-sen University, 510080 Guangzhou, ChinaDepartment of Obstetrics and Gynecology, The First Affliated Hospital, Sun Yat-sen University, 510080 Guangzhou, ChinaDepartment of Obstetrics and Gynecology, Peking University Third Hospital, 100191 Beijing, ChinaDepartment of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, 100191 Beijing, China; National Clinical Research Center for Obstetrics and Gynecology, 100191 Beijing, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, 100191 Beijing, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, 100191 Beijing, China; Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, 100191 Beijing, China; Corresponding authors at: Reproductive Medical Center, Department of Obstetrics and Gynecology, Peking University Third Hospital, Key Laboratory of Assisted, Beijing 100191, China (J. Qiao).Department of Obstetrics and Gynecology, Peking University Third Hospital, 100191 Beijing, China; Corresponding authors at: Reproductive Medical Center, Department of Obstetrics and Gynecology, Peking University Third Hospital, Key Laboratory of Assisted, Beijing 100191, China (J. Qiao).Introduction: The prognosis for cervical cancer (CC) patients with lymph node metastasis (LNM) is extremely poor. Lipid droplets (LDs) have a pivotal role in promoting tumor metastasis. The crosstalk mechanism between LDs and LNM modulated in CC remains largely unknown. Objectives: This study aimed to construct a miRNA-dependent progonostic model for CC patients and investigate whether miR-532-5p has a biological impact on LNM by regualting LDs accumulation. Methods: LASSO-Cox regression was applied to establish a prognostic prediction model. miR-532-5p had the lowest P-value in RNA expression (P < 0.001) and prognostic prediction (P < 0.0001) and was selected for further study. The functional role of the prognostic miR-532-5p-correlated competing endogenous RNA (ceRNA) network was investigated to clarify the crosstalk between LDs and LNM. The underlying mechanism was determined using site-directed mutagenesis, dual luciferase reporter assays, RNA immunoprecipitation assays, and rescue experiments. A xenograft LNM model was established to evaluate the effect of miR-532-5p and orlistat combination therapy on tumor growth and LNM. Results: A novel 5-miRNAs prognostic signature was constructed to better predict the prognosis of CC patient. Further study demonstrated that miR-532-5p inhibited epithelial-mesenchymal transition and lymphangiogenesis by regulating LDs accumulation. Interestingly, we also found that LDs accumulation promoted cell metastasis in vitro. Mechanistically, we demonstrated a miR-532-5p-correlated ceRNA network in which LINC01410 was bound directly to miR-532-5p and effectively functioned as miR-532-5p sponge to disinhibit its target gene-fatty acid synthase (FASN). Combined therapy with miR-532-5p and FASN inhibitor-orlistat further inhibited tumor growth and LNM in vivo. Conclusion: Our findings highlight a LD accumulation-dependent mechanism of miR-532-5p-modulated LNM and support treatment with miR-532-5p/orlistat as novel strategy for treating patients with LNM in CC.http://www.sciencedirect.com/science/article/pii/S2090123221001909miRNA prognostic modelLipid dropletFASNLymph node metastasisCervical cancer |
| spellingShingle | Chunliang Shang Yuan Li Tianhui He Yuandong Liao Qiqiao Du Pan Wang Jie Qiao Hongyan Guo The prognostic miR-532-5p-correlated ceRNA-mediated lipid droplet accumulation drives nodal metastasis of cervical cancer Journal of Advanced Research miRNA prognostic model Lipid droplet FASN Lymph node metastasis Cervical cancer |
| title | The prognostic miR-532-5p-correlated ceRNA-mediated lipid droplet accumulation drives nodal metastasis of cervical cancer |
| title_full | The prognostic miR-532-5p-correlated ceRNA-mediated lipid droplet accumulation drives nodal metastasis of cervical cancer |
| title_fullStr | The prognostic miR-532-5p-correlated ceRNA-mediated lipid droplet accumulation drives nodal metastasis of cervical cancer |
| title_full_unstemmed | The prognostic miR-532-5p-correlated ceRNA-mediated lipid droplet accumulation drives nodal metastasis of cervical cancer |
| title_short | The prognostic miR-532-5p-correlated ceRNA-mediated lipid droplet accumulation drives nodal metastasis of cervical cancer |
| title_sort | prognostic mir 532 5p correlated cerna mediated lipid droplet accumulation drives nodal metastasis of cervical cancer |
| topic | miRNA prognostic model Lipid droplet FASN Lymph node metastasis Cervical cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2090123221001909 |
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