SNHG17 Interacts with LRPPRC to Stabilize c-Myc and Promote G1/S Transition and Cell Proliferation

Long non-coding RNAs (lncRNAs) emerge as new regulators of various cell activities. The G1 to S phase (G1/S) transition is the key step that drives cell to the division cycle, and its dysregulation contributes to unrestrained cell proliferation and consequent tumor development.In this study, we examined lncRNA expression profiles during cell cycle using serum starvation-stimulation model in human skin fibroblasts (SFs) and identified that lncRNA SnoRNA Host Gene 17 (SNHG17) was elevated at the early G1 phase and in hepatocellular carcinoma (HCC) tissues. Both gain- and loss-of function studies disclosed that SNHG17 increased c-Myc protein level, accelerated G1/S transition and cell proliferation, and consequently promoted tumor growth. Up-regulation of SNHG17 was correlated with high c-Myc level in human HCC. Mechanistically, the 1-150-nt of SNHG17 physically interacted with the 1035-1369-aa of leucine rich pentatricopeptide repeat containing (LRPPRC) protein, and disrupting this interaction abrogated the promoting role of SNHG17 in c-Myc up-regulation, G1/S transition and cell proliferation. And the proliferation-stimulatory effect of SNHG17 was abrogated by silencing c-Myc or LRPPRC. Furthermore, silencing SNHG17 or LRPPRC increased the ubiquitylated c-Myc level and reduced c-Myc stability, suggesting that SNHG17 may inhibit c-Myc ubiquitination and thus enhance c-Myc level and facilitate proliferation by interacting with LRPPRC. Our findings identify a novel SNHG17-LRPPRC-c-Myc regulatory axis and elucidate its roles in G1/S transition and tumor growth, which provide potential targets for cancer therapy. Human primary skin fibroblasts （SFs）were isolated from human neonatal foreskin and cultured in RPMI 1604 medium supplemented with 10% FBS , 100 mg/mL streptomycin and 100 U/mL penicillin in a humidified atmosphere with 5% CO2 at 37 ℃. SFs were induced to enter a quiescent state by depriving serum for 48 hours and then stimulated to enter the G1 phase and subsequent S phase by adding serum. RNA Sequecing was performed in biological duplicates for SFs at 0, 4, and 18 hours after serum re-addition.