In recent decades, the incidence rate of papillary thyroid carcinoma (PTC) has been rapidly increasing. However, the molecular mechanism of the physiological and pathological processes of PTC is still largely unknown. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a tumor suppressor and exerts anti-tumor effect in several human cancers, while the role and underlying mechanism of LHPP in PTC remain vague. In this study, we firstly evaluated the roles of LHPP in PTC and explored its underlying mechanism. Using clinical tissue samples, we detected the level of LHPP in PTC tissues and in matched adjacent normal tissues. Lower level of LHPP was found in PTC tissues than in matched adjacent normal tissues. Similar LHPP expression pattern was found in PTC cell lines when compared with that in normal human thyroid follicular epithelial cells. Then, we over-expressed LHPP in three PTC cell lines and results showed that ectopic LHPP expression consistently reduced cell viability, proliferation, and migration and triggered cell autophagy. Furthermore, over-expression of LHPP inhibited the activation of the AKT/mTOR pathway and promoted the AMPK signaling pathway. In addition, the activation of AKT/mTOR and inhibition of AMPK signaling pathways restored the role of ectopic LHPP expression in PTC cell lines, indicating that LHPP exerts its anti-tumor activity through regulating the AKT/AMPK/mTOR pathway. Ultimately, we illustrated that ectopic LHPP expression inhibited PTC tumor growth in vivo. In conclusion, we revealed that LHPP has an anti-tumor effect in PTC and indicated that LHPP might serve as an effective diagnostic and therapeutic target for PTC.

中文翻译：

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LHPP通过调节AKT / AMPK / mTOR信号通路抑制甲状腺乳头状癌的细胞生长和迁移并触发自噬。

近几十年来，乳头状甲状腺癌（PTC）的发病率一直在迅速增加。但是，PTC的生理和病理过程的分子机制仍是未知之数。磷酸赖氨酸磷酸组氨酸无机焦磷酸磷酸酶（LHPP）是一种肿瘤抑制因子，在多种人类癌症中发挥抗肿瘤作用，而LHPP在PTC中的作用和潜在机制仍然不清楚。在这项研究中，我们首先评估了LHPP在PTC中的作用，并探讨了其潜在机制。使用临床组织样本，我们检测了PTC组织和匹配的相邻正常组织中LHPP的水平。在PTC组织中发现的LHPP水平低于匹配的相邻正常组织。与正常人甲状腺滤泡上皮细胞相比，在PTC细胞系中发现了相似的LHPP表达模式。然后，我们在三种PTC细胞系中过表达LHPP，结果表明异位LHPP表达持续降低细胞活力，增殖和迁移并触发细胞自噬。此外，LHPP的过表达抑制了AKT / mTOR通路的激活并促进了AMPK信号通路。此外，AKT / mTOR的激活和AMPK信号通路的抑制恢复了异位LHPP在PTC细胞系中的表达，表明LHPP通过调节AKT / AMPK / mTOR通路发挥其抗肿瘤活性。最终，我们阐明了异位LHPP表达在体内抑制了PTC肿瘤的生长。结论，