人源长寿保障基因2（LASS2）在多种恶性肿瘤中发挥抑癌作用，但具体机制尚不清楚。我们前期研究首次报道LASS2在甲状腺乳头状癌（PTC）组织表达低于癌旁及结节性甲状腺肿组织，且与PTC临床特征相关。此外，LASS2过表达抑制BCPAP细胞增殖、促进细胞凋亡。进一步研究提示LASS2可能与线粒体嵴重构有关，但分子机制不明。基于此，我们假设LASS2可能通过MICOS/线粒体复合物介导的ROS信号抑制甲状腺癌(TC)。本研究拟以不同TC细胞、荷瘤小鼠模型进一步探讨LASS2抑制TC的分子机制，研究内容主要涉及：（1）明确LASS2对TC细胞表型、ROS、线粒体嵴重构的调控作用；（2）运用荷瘤小鼠模型评价LASS2的抗肿瘤效力；（3）明确LASS2调控MICOS或线粒体复合物的作用方式与关键蛋白。这一假设的证实将首次揭示LASS2抑制TC发展的分子机制，为TC分子靶向治疗提供新思路。

LAG1 Longevity Assurance Homolog 2 (LASS2) plays an anti-tumor role in many malignant tumors, but the specific mechanisms remain unclear. Our previous studies reported for the first time that the expression of LASS2 was downregulated in papillary thyroid carcinoma (PTC) tissues compared with adjacent thyroid tissues or nodular goiter tissues. In addition, the expression of LASS2 was found to be associated with clinicopathological parameters of PTC. Overexpression of LASS2 significantly inhibited proliferation and promoted apoptosis in BCPAP cells. LAG1 Longevity Assurance Homolog 2 (LASS2) plays an anti-tumor role in many malignant tumors, but the specific mechanisms remain unclear. Our previous studies reported for the first time that the expression of LASS2 was downregulated in papillary thyroid carcinoma (PTC) tissues compared with adjacent thyroid tissues or nodular goiter tissues. In addition, the expression of LASS2 was found to be associated with clinicopathological parameters of PTC. Overexpression of LASS2 significantly inhibited proliferation and promoted apoptosis in BCPAP cells. Further studies indicated that LASS2 may be related to mitochondrial cristae remodeling, the molecular mechanism remains unclear. Based on these, we hypothesize that LASS2 may inhibit TC via ROS signal mediated by MICOS/mitochondrial complexes. In this study, different TC cell lines and nude mice tumor-bearing models were used to further explore the molecular mechanism of LASS2 in inhibiting TC. The main contents of this study were: (1) To clarify the regulatory effects of LASS2 on TC cell biology, ROS and mitochondrial cristae remodeling; (2) To evaluate the anti-tumor effect of LASS2 by using nude mice tumor-bearing models; (3) To clarify the mode of LASS2 regulating MICOS or mitochondrial complexes and key proteins. The confirmation of this hypothesis will reveal for the first time the molecular mechanism of LASS2 inhibiting TC development and provide new ideas for molecular targeted therapy of thyroid cancer.