Song Kun, Li Bin, Chen Ying-Ying, Wang Hua, Liu Kang-Cheng, Tan Wei, Zou Jing
Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
Mol Ther Oncolytics. 2021 Jun 24;22:582-591. doi: 10.1016/j.omto.2021.06.009. eCollection 2021 Sep 24.
Retinoblastoma (RB) is the most common intraocular tumor among children. Leucine-rich pentatricopeptide repeat (PPR)-motif-containing protein (LRPPRC), a suppressor gene of autophagy, has been proven to play a regulatory role in tumor progression. However, little is known about functional roles and mechanisms of LRPPRC in RB progression. First, we performed a detailed analysis for RB and normal control. The expression of LRPPRC in the RB tissues was significantly higher than that in normal tissues. Moreover, LRPPRC suppression could repress tumor cell migration, invasion, glycolysis, and reactive oxygen species (ROS)/hypoxia-inducible factor-1α (HIF1-α) pathway activation by mediating autophagy. Furthermore, overexpression of HIF1-α partially reversed the above changes induced by LRPPRC knockdown. The regulation of LRPPRC on tumor metastasis and glycolysis was also validated by a xenograft tumor assay. In summary, LRPPRC could regulate metastasis and glycolysis of RB by mediating autophagy suppression and further activating the ROS/HIF1-α pathway, and LRPPRC could be a promising prognostic biomarker for RB.
视网膜母细胞瘤（RB）是儿童中最常见的眼内肿瘤。富含亮氨酸的五肽重复序列（PPR）基序蛋白（LRPPRC）作为一种自噬抑制基因，已被证实在肿瘤进展中发挥调节作用。然而，关于LRPPRC在RB进展中的功能作用和机制知之甚少。首先，我们对RB组织和正常对照进行了详细分析。LRPPRC在RB组织中的表达明显高于正常组织。此外，LRPPRC抑制可通过介导自噬来抑制肿瘤细胞迁移、侵袭、糖酵解以及活性氧（ROS）/缺氧诱导因子-1α（HIF1-α）途径的激活。此外，HIF1-α的过表达部分逆转了LRPPRC敲低所诱导的上述变化。LRPPRC对肿瘤转移和糖酵解的调节作用也通过异种移植肿瘤实验得到了验证。总之，LRPPRC可通过介导自噬抑制并进一步激活ROS/HIF1-α途径来调节RB的转移和糖酵解，并且LRPPRC可能是一种有前景的RB预后生物标志物。
