Mechanistic Study Of Long Non-coding RNA SNHG17 On The Cell Proliferation And Metastasis Of Colorectal Cancer

Objective:The main purpose of this project is to study the role of long non-coding RNAs(lncRNA)-small nucleolar RNA host gene 17(SNHG17)on cell proliferation and metastasis in colorectal cancer(CRC)and explore its mechanism preliminarily.Methods: Quantitative reverse transcription PCR(RT-qPCR)was used to detect the expression levels of SNHG17 in CRC tissues and cells.CCK-8 and clony formation assays were used to detect the proliferation ability of SNHG17 on CRC cells in vitro.Transwell experiments was performed to observe the effects of SNHG17 on the migration and invasion of CRC cells.The in vivo influence of SNHG17 on tumor growth was studied by subcutaneous tumorigenesis in nude mice.According to the RNA pull down experiment combined with mass spectrometry analyses,potential binding proteins of SNHG17 were screened out.Western blot and RNA immunoprecipitation were used to verify the binding of SNHG17 to its potential target proteins.The expression levels of the target protein in CRC tissues were then analyzed using immunohistochemistry.Finally,the interaction between SNHG17 and the target protein was verified again by the function recovery experiment.Results: Compared with adjacent tissues,the expression levels of SNHG17 in CRC tissues were significantly higher(P < 0.0001),and the high expression of SNHG17 was closely related to poor prognosis(log rank = 10.57,P = 0.0012).The results of functional experiments showed that overexpression of SNHG17 significantly promoted the proliferation,migration and invasion of CRC cells;whereas the proliferation,migration and invasion of CRC cells were inhibited after knocking down the expression of SNHG17.The results of animal experiments showed that overexpression of SNHG17 could promote tumor growth and metastasis in vivo,whereas SNHG17 knockdown inhibited tumor growth and metastasis in vivo.In terms of mechanism,based on the results of RNA pull down and mass spectrometry analyses,we identified that pescadillo ribosomal biogenesis factor 1(PES1)function as the target protein of SNHG17.SNHG17 markedly increased the half-life of PES1 in HCT116 cells.Silencing SNHG17 expression reduced the half-life of PES1 in Lo Vo cells.Immunohistochemistry results showed that PES1 was overexpressed in CRC tissues and positively correlated with the expression of SNHG17(P < 0.05).Functional recovery experiments proved that knockdown of PES1 blocked the promoting effect of SNHG17 on the cell proliferation and migration of CRC cells.Conclusion: SNHG17 acts as an oncogene in CRC to promote the proliferation,migration and invasion of CRC cells.SNHG17 competes with Trim23 to bind PES1,inhibits its ubiquitination degradation and promotes the development of CRC.