Studies on the Carcinogenic Mechanisms of Serine/Threonine-Protein Kinase (Sik3) Involved in the Process of Breast Tumor Formation

Based on the analysis of clinical breast cancer tissue specimens and cancer gene atlas database, it was found that SIK3 is the target of breast cancer oncogenic molecules.。The reasons are: firstly, cancer tissue (T) mRNA performance is higher than normal (N) tissue. Secondly, SIK3 is higher in TNBC breast cancer cell lines. Thirdly, overexpression of SIK3 (pcDNA3) cells makes cells grow rapidly and up-regulates cell cycle related proteins. Fourthly, mRNA sequencing results show that SIK3 overexpresses stable cell lines, significantly up- regulates cell cycle, metastasis and drug resistance related genes. Fifthly, SIK3 overexpression reduces clinical drug efficacy. The importance of SIK3 needs further exploration.(Year-1): Confirms that SIK3 is a novel molecular target for breast cancer carcinogenesis. # Confirm the correlation of SIK3 gene expression with breast cancer specimens, clinical medical records, and genomic map database.# Study the expression of SIK3 is related to the carcinogenesis of breast cancer cell lines with different receptor expressions.# Study the mechanism of SIK3 cell lines with different receptor expression morphology on breast cancer.(Year-2): SIK3 gene expression characteristics and functional analysis of breast cancer formation# The molecular mechanism of SIK3 in breast cancer growth was confirmed by SIK3 inhibition (si RNA), knockout (CRISPR / Cas9), and overexpressing cell lines.# Combining changes in the SIK3 gene and clinical breast cancer treatment drugs (chemotherapy / targeting) to explore its synergistic effects and related mechanisms.# Screening SIK3 inhibitors and their potential for combined treatment of breast cancer by using cell line models.(Year-3): In vivo animal model to explore the carcinogenesis mechanism of SIK3 and translational study of anti-cancer drug therapy# SIK3 inhibits and overexpresses stable cell lines and cell line derived Xenograft studies to confirm the carcinogenic role of SIK3 in vivo.# SIK3 inhibits and overexpresses stable cell lines and cell line derived Xenograft studies to confirm the synergistic effects in vivo.# Patient-derived xenograft (PDX) tumor animal model confirms that SIK3 affects breast cancer drug treatment.