The Effect And Mechanism Of Retinol Metabolism Related Genes LRAT/RDH12 In The Progress Of Squamous Cervical Cancer

Cervical cancer is one of the most common cancers in females, HPV infection and genes related in tumor growth are critical for the progress of cervical cancer. Our studies have screened the differential expressed genes between squamous cervical carcinoma and matched adjacent non-tumor tissues by RNA-Seq technology for the first time. qRT-PCR, Western blot and immunochemistry were used to validate the expression of differential expressed genes. We discovered that the expression of the retinol metabolism related genes (LRAT and RDH12) were lower in squamous cervical carcinoma tissues and cells than that of matched adjacent non-tumor tissues and normal cervical squamous epithelial cells. In our preliminary experiments, it has been found that in the human squamous cervical cancer cells with overexpression of LRAT、RDH12, the expression of proteins involved in MAPK/NF-κB signal pathway changed accordingly. In this study, we are trying to examine the effect of LRAT, RDH12 genes on proliferation, apoptosis, migration, invasion, as well as tumor growth and metastasis of cervical cancer through p38 MAPK/NF-κB signal pathway in cultured cells and nude mouse model, and analyse the relationship between LRAT、RDH12 genes and the clinical pathological factors of cervical squamous carcinoma. This project aims to clarify the effect and mechanism of retinol metabolism related genes LRAT/RDH12 in the progress of squamous cervical cancer and provide important theoretical supports and molecular targets for squamous cervical carcinoma.Firstly, we furtherly demonstrated that the expression of LRAT、RDH12 in the cancer tissue is below the level of that in para-cancer tissue. we successfully constructed the overexpression vector of LRAT、RDH12. LRAT、RDH12 overexpression inhibited the cell proliferation, transferation and invation,and promoted the apoptosis leading the block of the cell cycle.Besides,we found that as the expression of LRAT、RDH12increased, the expression of p38 MAPK/NF-κB decreased.when we inhibit the expression of p38 MAPK,the expression level of p50、p65 NF-κB decreased,,and the expression of LRAT、RDH12 remained the same. when we inhibited the expression of p50、p65 NF-κB,the expression level of LRAT、RDH12 and p38 MAPK didn’t change. Therefore, we knew that LRAT、RDH12 located the upstream of the MAPK/NF-κB pathway, the inhibition effect of cervical cancer was related to the inhibition to the MAPK/NF-κB pathway.In conclusion, overexpression of LRAT、RDH 12 helps inhibiting the cell proliferation, transferation and invation,and promoted the apoptosis leading the block of the cell cycle. LRAT、RDH12 located the upstream of the MAPK/NF-κB pathway, the inhibition effect of cervical cancer was related to the inhibition to the MAPK/NF-κB pathway, which will help to establish more efficient chemotherapies for cervical cancer.