The Study On The Effect Of TMEM147 On Proliferation,Invasion And Metastasis And Tumor-associated-macrophage M2 Polarization Of Hepatocellular Carcinoma

Background and PurposeHepatocellular carcinoma(HCC)is the sixth most common cancer worldwide,and the fourth leading cause of cancer-related death globally and it accounts for 75%to 85% of primary liver cancers.The occurrence and development of HCC is highly related to the chronic inflammatory process,and the tumor immune microenvironment plays an important role in tumor development,of which tumor-associated macrophages(TAM)are key players.TAMs can be polarized into different functional phenotypes,among which M2 TAMs have tumor-promoting effects,and M1 TAMs have anti-tumor functions.Compared with other solid tumors,liver cancer has a lower sensitivity to radiotherapy and chemotherapy,and its treatment mainly relies on surgery,resulting in a poor prognosis.In order to improve the treatment of liver cancer and obtain a better prognosis,researchers are now paying more attention to the molecular mechanism and immunology of liver cancer.The function of transmembrane protein 147(TMEM147)has not been fully elucidated,and studies have confirmed that it is closely related to bladder cancer,colon cancer,rheumatoid arthritis and other diseases.The main purpose of this research is to verify and analyze the effect of TMEM147 on the proliferation,invasion,metastasis and TAM polarization of HCC.MethodsFor human normal liver tissue and cell line and a variety of HCC tissue and cell lines,Real time PCR and Western Blot assays were used to detect the differences in the expression levels of TMEM147;After stably over-expressed or silenced expression,the transfected HCC cells were subjected to CCK8 assay and clone formation assay to examine the changes in their proliferation ability,and the wound-healing assay and transwell assay were used to examine the changes in their invasion and migration abilities.Finally,the effect of different TMEM147 expression HCC cells on TAM polarization was detected by in vitro co-culture technology,Real time PCR and Western Blot assays.ResultsCompared with human normal liver tissue and cell line,TMEM147 was highly expressed in HCC cell lines;further experiment results on the proliferation,invasion and metastasis of HCC cells showed that overexpression of TMEM147 promotes the ability of HCC cells’ proliferation,invasion and migration abilities.On the contrary,Silencing TMEM147 inhibits the proliferation,invasion and migration abilities of HCC cells.At the same time,TMEM147-overexpressed HCC cells co-cultured with TAM in vitro can promote the M2 polarization of TAM more than TMEM147-silenced HCC cells.ConclusionsCompared with normal liver tissue and cell line,TMEM147 is highly expressed in various HCC cell lines in vitro.TMEM147 has the ability to promote the invasion and migration of HCC cells,and TMEM147 in liver cancer cells can promote the M2 polarization of TAM.TMEM147 is expected to be a significant indicator for evaluating the prognosis of HCC.Intervention of TMEM147 expression may be an effective treatment option to delay the progression of HCC and improve the prognosis of HCC.