Journal of Interferon & Cytokine Research

Nucleosome Assembly Protein 1-Like 3 Enhances Cisplatin Resistance of Ovarian Cancer Cell by Activating Transforming Growth Factor-Beta Pathway

Chemotherapy resistance is one of the main reasons for tumor-related death. In particular, ovarian cancer patients often acquire drug resistance after chemotherapy. In this study, we found that the histone chaperone, nucleosome assembly protein 1-like 3 (NAP1L3), was significantly upregulated in tissues with cisplatin resistance compared with cisplatin-sensitive tissues. Patients with high NAP1L3 levels had poor prognosis, suggesting that NAP1L3 might regulate ovarian cancer resistance. Colony formation and terminal deoxynulceotidyl transferase nick-end-labeling (TUNEL) assays showed cells with high NAP1L3 had high cisplatin resistance, whereas cells with low NAP1L3 had poor cisplatin resistance. NAP1L3 overexpression significantly increased cisplatin resistance, whereas NAP1L3 knockdown significantly reduced cisplatin resistance, suggesting that NAP1L3 promoted cisplatin resistance. Mechanistically, gene set enrichment analysis and luciferase reporter assays showed that NAP1L3 regulated the transforming growth factor-beta (TGF-β) pathway. NAP1L3 overexpression increased the phosphorylation and nuclear translocation of SMAD family member 2 (SMAD2) and SMAD3, confirming that NAP1L3 activated the TGF-β pathway. Therefore, NAP1L3 might represent a novel target to overcome ovarian cancer chemoresistance.

Long Noncoding RNA LINC00899/miR-944/ESR1 Axis Regulates Cervical Cancer Cell Proliferation, Migration, and Invasion

Cervical cancer (CC) is a common malignancy in women. Long noncoding RNA LINC00899 plays a role in cancer, but its effects in CC are unknown. Our experiment aims to investigate the specific effects of LINC00899 in CC. LINC00899 was lowly expressed in CC tissues and cells, and overexpressed LINC0089 inhibited the viability, proliferation, migration, and invasion of CC cells, whereas silencing of LINC00899 had the opposite effect. There is a targeting relationship between LINC0089 and miR-944. It was found that miR-944 could competitively bind with LINC00899, and LINC00899 in turn, could downregulate expression of miR-944. Moreover, estrogen receptor 1 (ESR1) was the target gene of miR-944. Overexpressed miR-944 inhibited ESR1 expression, yet enhanced the migration and invasion of CC cells and promoted the expression levels of N-cadherin and Vimentin while inhibiting the expression of E-cadherin. However, overexpressed ESR1 reversed the effect of miR-944 overexpression on CC cells. LINC00899/miR-944/ESR1 axis regulates the proliferation, migration, and invasion of CC cells by regulating the expression levels of related proteins.

CCDC68 Upregulation by IL-6 Promotes Endometrial Carcinoma Progression

The elevation of circulating interleukin 6 (IL-6) is one of the major molecular characteristics of endometrial carcinoma. In this study, we investigated the role of coiled-coil domain-containing 68 (CCDC68) in IL-6-associated endometrial carcinoma progression. CCDC68 expression levels and the activation of IL-6 pathway were detected by qPCR and Western blot. Stable CCDC68 knockdown Ishikawa and RL-95 cells were created to investigate cancer cell proliferation, migration, and invasion with or without IL-6 administration. Kaplan-Meier's analysis was used to determine the correlation between CCDC68 expression and overall survival or recurrence-free survival in endometrial carcinoma patients. CCDC68 expression level is significantly uregulated by IL-6 stimulation. Increased CCDC68 expression predicts poor prognosis in endometrial carcinoma patients. CCDC68 knockdown dramatically inhibit IL-6-associated cancer cell proliferation, migration, invasion, and downregulate the expression of proto-oncogenes in endometrial carcinoma cells. CCDC68 acts as a cancer-promoting factor in IL-6-stimulated endometrial carcinoma cells, and blocking the expression of CCDC68 might be a novel therapeutic strategy for the endometrial carcinoma treatment.