Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Cell Death Dis. 2022 Jan 10;13(1):43. doi: 10.1038/s41419-021-04492-z.
RSL1D1 (ribosomal L1 domain containing 1), a member of the universal ribosomal protein uL1 family, was suggested to be a new candidate target for colorectal cancer (CRC). However, the role of RSL1D1 in cancer, including CRC, remains largely elusive. Here, we demonstrated that RSL1D1 expression was significantly elevated in tumors from CRC patients and that high expression of RSL1D1 was correlated with poorer survival of CRC patients. Functionally, RSL1D1 promoted the proliferation, invasion, and metastasis of CRC cells by suppressing autophagy. Interestingly, RSL1D1 interacted with RAN and inhibited its deacetylation by competitively binding with Sirt7. By affecting the acetylation of RAN, RSL1D1 inhibited the accumulation of nuclear STAT3 and the STAT3-regulated autophagic program. Taken together, our study uncovered the key role of the RSL1D1/RAN/STAT3 regulatory axis in autophagy and tumor progression in CRC, providing a new candidate target for CRC treatment.
RSL1D1（核糖体 L1 结构域包含 1）是普遍核糖体蛋白 uL1 家族的成员，被认为是结直肠癌（CRC）的新候选靶标。然而，RSL1D1 在癌症中的作用，包括 CRC，仍然很大程度上难以捉摸。在这里，我们证明了 RSL1D1 在 CRC 患者的肿瘤中表达显著升高，并且 RSL1D1 的高表达与 CRC 患者的生存不良相关。功能上，RSL1D1 通过抑制自噬促进 CRC 细胞的增殖、侵袭和转移。有趣的是，RSL1D1 与 RAN 相互作用，并通过与 Sirt7 竞争结合来抑制其去乙酰化。通过影响 RAN 的乙酰化，RSL1D1 抑制了核 STAT3 的积累和 STAT3 调节的自噬程序。总之，我们的研究揭示了 RSL1D1/RAN/STAT3 调节轴在 CRC 中自噬和肿瘤进展中的关键作用，为 CRC 治疗提供了一个新的候选靶点。
