DCTPP1, an Oncogene Regulated by miR-378a-3p, Promotes Proliferation of Breast Cancer via DNA Repair Signaling Pathway

Abstract

Breast cancer (BRCA) is one of the most deadly cancers worldwide, with poor survival rates that could be due to its high proliferation. Human all-alpha dCTP pyrophosphatase 1 (DCTPP1) is implicated in numerous diseases, including cancers. However, its role in BRCA is unclear. In this study, we used bioinformatic analyses of the ONCOMINE, UALCAN, and GEPIA databases to determine the expression pattern of DCTPP1 in BRCA. We found that elevated DCTPP1 levels correlate with poor BRCA prognosis. DCTPP1 silencing inhibited BRCA cell proliferation and induced apoptosis in vitro, as well as in vivo. Our data show that this tumorigenic effect depends on DNA repair signaling. Moreover, we found that DCTPP1 is directly modulated by miR-378a-3p, whose downregulation is linked to BRCA progression. Our results showed down-regulation of miR-378a-3p in BRCA. Upregulation of miR-378a-3p, on the other hand, can inhibit BRCA cell growth and proliferation. This study shows that reduced miR-378a-3p level enhances DCTPP1 expression in BRCA, which promotes proliferation by activating DNA repair signaling in BRCA.

ROS-Induced DCTPP1 Upregulation Contributes to Cisplatin Resistance in Ovarian Cancer

“…First, we used lentivirus to deliver shRNA targeting DCTPP1 to construct the DCTPPI knockdown cell model of ovarian cancer cells. Through the cell models, we have observed that DCTPP1 is a promoter for the growth of ovarian cancer, which is consistent with the finding in prostate cancer and gastric cancer ( Marquard and Jucker, 2020 ; Niu et al, 2021 ). With DCTPP1 knockdown, ovarian cancer cells showed growth inhibition both in vivo and in vitro .…”

“…DCTTP1 exhibits nucleic accumulation in multiple carcinomas ( Requena et al, 2014 ; Requena et al, 2016 ). Researches have shown that DCTPP1 promotes proliferation of breast cancer via DNA repair signaling pathway ( Requena et al, 2016 ; Xia et al, 2016 ; Niu et al, 2021 ). Recently, the regulatory function of DCTPP1 in drug response has gained attraction.…”

“…Recently, the regulatory function of DCTPP1 in drug response has gained attraction. DCTPP1 attenuates the sensitivity of human gastric cancer cells to 5-fluorouracil by up-regulating MDR1 expression epigenetically and DCTPP1 is involved in the cellular response to decitabine ( Xia et al, 2016 ; Niu et al, 2021 ). However, the role of DCTPP1 in response to cisplatin in ovarian cancer cells remains largely unknown.…”

Construction and Validation of a Prognostic Model Based on mRNAsi-Related Genes in Breast Cancer

“…Similarly, HMGB3 is also a prototypical marker of breast cancer progression but worsens cancer progression primarily by promoting formation of breast layers of breast cancer cells [ 40 , 41 ]. DCTPP1 is an oncogene regulated by the oncogenic factor miR-378a-3p, and this gene facilitates breast cancer cell proliferation through the interference of DNA repair signaling pathway [ 42 , 43 ]. The phenomenon of overexpression of SHCBP1 in breast cancer has been studied, and cellular experiments have demonstrated that this gene directly regulates breast cancer cell proliferation and promotes the cell cycle [ 44 ].…”

Development and Validation of Ferroptosis-Related lncRNAs as Prognosis and Diagnosis Biomarkers for Breast Cancer

“…The main treatments for BC are surgery with adjuvant radiation therapy and chemotherapy [14][15][16][17][18]. However, many BC patients are resistant to chemotherapy, endocrine, and targeted therapy, and these patients generally have poor survival rates [6,[19][20][21][22][23][24]. The complexity and high heterogeneity of the underlying mechanisms of BC make its treatment difficult [25][26][27][28][29].…”