Abstract
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.
Highlights
Colorectal cancer (CRC) is a type of gastrointestinal cancer with high morbidity and mortality [1]
RSL1D1 is highly expressed in tumor samples from CRC patients, and high expression of RSL1D1 is correlated with poor CRC prognosis The mRNA and protein expression levels of RSL1D1 were studied in 6 CRC cell lines (SW480, SW620, LoVo, DLD1, HCT116, and RKO), 1 intestinal epithelial cell line (NCM460) and paired CRC tissues with normal counterparts using quantitative reverse transcriptionpolymerase chain reaction and Western blot (WB) assays
We further analyzed the mRNA expression of RSL1D1 in CRC samples using Gene Expression Profiling Interactive Analysis (GEPIA) public data [19], and the results showed that the expression of RSL1D1 mRNA in CRC tumor tissues was higher than that in normal intestinal tissues (P < 0.01, Fig. 1C)
Summary
Colorectal cancer (CRC) is a type of gastrointestinal cancer with high morbidity and mortality [1]. Targeted therapy and immunotherapy have greatly improved the CRC treatments in recent years [2,3,4], tumor recurrence and metastasis represent the main causes of cancer-related death. It is critical to identify additional key targets in CRC progression and metastasis. RSL1D1, which contains part of the ribosomal L1p/L10e consensus sequence in its N-terminus and a long lysine-rich domain in its C-terminus, was suggested as a candidate target for CRC [5]. As an inhibitor of cellular senescence, RSL1D1 is highly expressed in liver, prostate, and breast cancers, suggesting that it may be closely related to the pathogenesis and progression of many cancers [10,11,12]. The role of RSL1D1 in CRC is still unclear
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