LRPPRC regulates metastasis and glycolysis by modulating autophagy and the ROS/HIF1-α pathway in retinoblastoma

Kun Song; Bin Li; Ying-Ying Chen; Hua Wang; Kang-Cheng Liu; Wei Tan; Jing Zou

doi:10.1016/j.omto.2021.06.009

LRPPRC regulates metastasis and glycolysis by modulating autophagy and the ROS/HIF1-α pathway in retinoblastoma

Mol Ther Oncolytics. 2021 Jun 24:22:582-591. doi: 10.1016/j.omto.2021.06.009. eCollection 2021 Sep 24.

Authors

Kun Song¹, Bin Li², Ying-Ying Chen³, Hua Wang^{4

5}, Kang-Cheng Liu^{4

5}, Wei Tan^{4

5}, Jing Zou^{4

5}

Affiliations

¹ Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
³ Department of Ophthalmology, Hainan General Hospital, Haikou 570000, Hainan Province, China.
⁴ Eye Center of Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
⁵ Hunan Key Laboratory of Ophthalmology, No. 87 Xiangya Road, Kaifu District, Changsha 410008, Hunan Province, China.

Abstract

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.

Keywords: LRPPRC; ROS/HIF1-α pathway; autophagy; glycolysis; metastasis; retinoblastoma.