Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma
Abstract Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-12-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06348-0 |
| _version_ | 1797388046633533440 |
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| author | Xiaoping Zhang Yong Zhong Lin Liu Chengyou Jia Haidong Cai Jianshe Yang Bo Wu Zhongwei Lv |
| author_facet | Xiaoping Zhang Yong Zhong Lin Liu Chengyou Jia Haidong Cai Jianshe Yang Bo Wu Zhongwei Lv |
| author_sort | Xiaoping Zhang |
| collection | DOAJ |
| description | Abstract Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial function in PTC. We find that fasting impairs glycolysis and reduces mitochondrial dysfunction in vitro and in vivo and also fasting in vitro and fasting mimicking diets (FMD) in vivo significantly increase the expression of lncRNA-protein kinase C theta antisense RNA 1 (PRKCQ-AS1), during the inhibition of TPC cell glycolysis and mitochondrial function. Moreover, lncRNA PRKCQ-AS1 was significantly lower in PTC tissues and cells. In addition, PRKCQ-AS1 overexpression increased PTC cell glycolysis and mitochondrial function; PRKCQ-AS1 knockdown has the opposite effect. On further mechanistic analysis, we identified that PRKCQ-AS1 physically interacts with IGF2BPs and enhances protein arginine methyltransferases 7 (PRMT7) mRNA, which is the key player in regulating glycolysis and mitochondrial function in PTC. Hence, PRKCQ-AS1 inhibits tumor growth while regulating glycolysis and mitochondrial functions via IGF2BPs/PRMT7 signaling. These results indicate that lncRNA PRKCQ-AS1 is a key downstream target of fasting and is involved in PTC metabolic reprogramming. Further, the PRKCQ-AS1/IGF2BPs/PRMT7 axis is an ideal therapeutic target for PTC diagnosis and treatment. |
| first_indexed | 2024-03-08T22:34:05Z |
| format | Article |
| id | doaj.art-250abc3773854154947bf58be5e0ee64 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-08T22:34:05Z |
| publishDate | 2023-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-250abc3773854154947bf58be5e0ee642023-12-17T12:31:40ZengNature Publishing GroupCell Death and Disease2041-48892023-12-01141211510.1038/s41419-023-06348-0Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinomaXiaoping Zhang0Yong Zhong1Lin Liu2Chengyou Jia3Haidong Cai4Jianshe Yang5Bo Wu6Zhongwei Lv7Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People’s Hospital, Zhuhai hospital Affiliated with Jinan University, Jinan UniversityDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityCenter of Thyroid, Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityAbstract Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial function in PTC. We find that fasting impairs glycolysis and reduces mitochondrial dysfunction in vitro and in vivo and also fasting in vitro and fasting mimicking diets (FMD) in vivo significantly increase the expression of lncRNA-protein kinase C theta antisense RNA 1 (PRKCQ-AS1), during the inhibition of TPC cell glycolysis and mitochondrial function. Moreover, lncRNA PRKCQ-AS1 was significantly lower in PTC tissues and cells. In addition, PRKCQ-AS1 overexpression increased PTC cell glycolysis and mitochondrial function; PRKCQ-AS1 knockdown has the opposite effect. On further mechanistic analysis, we identified that PRKCQ-AS1 physically interacts with IGF2BPs and enhances protein arginine methyltransferases 7 (PRMT7) mRNA, which is the key player in regulating glycolysis and mitochondrial function in PTC. Hence, PRKCQ-AS1 inhibits tumor growth while regulating glycolysis and mitochondrial functions via IGF2BPs/PRMT7 signaling. These results indicate that lncRNA PRKCQ-AS1 is a key downstream target of fasting and is involved in PTC metabolic reprogramming. Further, the PRKCQ-AS1/IGF2BPs/PRMT7 axis is an ideal therapeutic target for PTC diagnosis and treatment.https://doi.org/10.1038/s41419-023-06348-0 |
| spellingShingle | Xiaoping Zhang Yong Zhong Lin Liu Chengyou Jia Haidong Cai Jianshe Yang Bo Wu Zhongwei Lv Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma Cell Death and Disease |
| title | Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma |
| title_full | Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma |
| title_fullStr | Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma |
| title_full_unstemmed | Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma |
| title_short | Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma |
| title_sort | fasting regulates mitochondrial function through lncrna prkcq as1 mediated igf2bps in papillary thyroid carcinoma |
| url | https://doi.org/10.1038/s41419-023-06348-0 |
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