LncRNA WFDC21P interacts with SEC63 to promote gastric cancer malignant behaviors by regulating calcium homeostasis signaling pathway.

BACKGROUND: Gastric cancer is currently estimated to be the fifth leading common cancer in the world, and responsible for about one million new cases and an estimated 769,000 cancer-related deaths each year. WFDC21P is long non-coding RNA and has been reported to play critical roles in serval types of cancer. Our research aims to investigate the biological effects and molecular mechanism of WFDC21P in gastric cancer. METHODS: Datasets (GSE53137, GSE58828, and GSE109476) in GEO database were used to screen differential expressed lncRNAs in gastric cancer by online GEO2R analysis tool. Quantitative RT-PCR was used to verify the above prediction in ten pairs of gastric cancer and corresponding paracancerous tissues. Pan-cancer analysis was used to analyze the expression of WFDC21P in different types of cancer. Small interfering RNAs were used to WFDC21P knockdown. CCK-8 and colony formation assays were used to measure the proliferation and tumorigenesis abilities. Wound healing and Transwell assay were used to detect the migration and invasion abilities. Proteins that interact with WFDC21P were predicted by catRAPID database. RNA pull down and RNA Immunoprecipitation were used to confirm the interaction. Western blotting was used to detect the key proteins level in calcium homeostasis signaling pathway. Loss-of-function and rescue assays were used to evaluate the biological function of SEC63 at the background of WFDC21P silencing. RESULTS: WFDC21P was upregulated in gastric cancer tissues and cell lines. WFDC21P downregulation suppressed proliferation, tumorigenesis, migration, invasion, and promoted apoptosis in gastric cancer. SEC63 protein had the capability to bind with WFDC21P and the expression of SEC63 was regulated by WFDC21P. SEC63 was also upregulated in gastric cancer and exerted effects during tumor growth and metastasis. CONCLUSIONS: This study confirmed that lncRNA WFDC21P aggravated gastric cancer malignant behaviors by interacting with SEC63 to regulate the calcium homeostasis signaling pathway.

Mps1 is associated with the BRAFV600E mutation and predicts poor outcome in patients with colorectal cancer.

Colorectal cancer (CRC) with the V600E mutation of B-Raf proto-oncogene serine/threonine kinase (BRAFV600E) mutation is insensitive to chemotherapy and is indicative of a poor patient prognosis. Although BRAF inhibitors have a marked effect on malignant melanoma harboring the BRAFV600E mutation, they have a limited effect on patients with CRC with the same BRAF mutation. A previous study identified a novel gene, monopolar spindle protein kinase 1 (Mps1), a downstream target of BRAFV600E only, rather than of wild-type BRAF as well, which contributes to tumorigenesis in melanoma. In the present study, the incidence of BRAFV600E in patients with CRC was identified and the correlation of Mps1, phospho-extracellular-signal-regulated kinase (p-ERK) and BRAFV600E was investigated. The results indicated that the mutation rate of BRAFV600E was 5.2% in CRC. Poorly differentiated tumors and mucinous tumors have a significantly higher incidence of BRAFV600E compared with well-differentiated tumors and non-mucinous tumors (P<0.05). Kaplan-Meier survival analysis indicated that the survival rate was markedly lower in patients with BRAFV600E compared with in patients with wild-type BRAF (BRAFWT). The expression of p-ERK and Mps1 in CRC with BRAFV600E was significantly higher compared with in CRC with BRAFWT (P<0.05), and their expression is associated with cancer classification, degree of differentiation and lymph node transfusion (P<0.05). In addition p-ERK expression was positively correlated with Mps1 expression, with a contingency coefficient of 0.679 (P=0.002). In conclusion, the results of the present study indicated that Mps1 was significantly associated with BRAFV600E/p-ERK and may serve a crucial function in the development of CRC. The results of the present study raise the possibility that targeting the oncogenic BRAF and Mps1, particularly when in conjunction, could provide promising therapeutic opportunities for the treatment of CRC.

Artesunate attenuates glioma proliferation, migration and invasion by affecting cellular mechanical properties.

Glioma is one of the most common malignant brain tumors. Current chemotherapy is far from providing satisfactory clinical outcomes for patients with glioma. More efficient drugs are urgently needed. Artesunate (ART) is clinically used as an anti-malarial agent and exhibits potent antiproliferative activity as a traditional Chinese medicine. In addition, ART has been shown to exert a profound cytotoxic effect on various tumor cell lines, presenting a novel candidate for cancer chemotherapy. However, its anticancer effect on glioma by altering cell biomechanical properties remains unclear. The present study aimed to identify the anticancer effects of ART on human glioma SHG44 cells by assessing cell proliferation, migration/invasion, the expression of claudin-1 and the biomechanical properties of ART-treated SHG44 cells. The proliferation of the SHG44 cells was assessed by MTT assay. The cell apoptosis was detected by flow cytometry. For cell migration and invasion assays, the Transwell was used. The expression of the gene claudin-1 was detected by polymerase chain reaction. The cell membrane and biomechanical properties, as targets of ART action, were investigated by atomic force microscopy (AFM). ART significantly inhibited the proliferation of SHG44 cells in a dose- and time-dependent manner. After treatment with 30 mg/l ART, the level of cell apoptosis was significantly increased (from 6.88±0.062 to 23.7±4.16%). Furthermore, the cell migration and invasion abilities of the SHG44 cells were markedly inhibited after treatment with 30 mg/l ART. Compared with the control group (0 mg/l ART), the SHG44 cells treated with 30 mg/l ART exhibited upregulated expression of claudin-1, increased adhesive force (from 2,400±300 to 3,600±500 pN), increased high connection among SHG44 cells, increased cytomembrane roughness (from 0.118±0.011 to 0.269±0.015 µm) and reduced elasticity (from 23±8 to 3.5±1.1 MPa). The present study demonstrated that ART could alter the biomechanical properties of the glioma cells to inhibit cell proliferation, migration and invasion.

Artesunate altered cellular mechanical properties leading to deregulation of cell proliferation and migration in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer in China. Artesunate (ART) is used clinically as an anti-malarial agent and exhibits potent antiproliferative activity. In addition, ART has demonstrated remarkable antitumor activity, presenting a novel candidate for cancer chemotherapy. However, its effect on ESCC remains unknown. The present study analyzed the antitumor effects of ART in the KYSE-150 ESCC line by assessing cell proliferation, cell death, cell migration/invasion and the biomechanical properties of ART-treated KYSE-150 cells. ART treatment significantly suppressed the proliferation of KYSE-150 cells in a dose- and time-dependent manner, as assessed by MTT assay. Following treatment with 30 mg/l ART, the cell population in the G0/G1 phase and the level of cell apoptosis significantly increased from 54±1.5 to 68.1±0.3%, and from 4.53±0.58 to 12.45±0.62%, respectively. Furthermore, the cell migration and invasion of KYSE-150 cells treated with 30 mg/l ART was markedly inhibited. The cell membrane and biomechanical properties were investigated using atomic force microscopy, as targets of ART action. ESCC cells treated with 30 mg/l ART exhibited increased adhesive force, increased cytomembrane roughness and reduced elasticity compared with the control group (KYSE-150 cells without ART treatment). The biomechanical properties of KYSE-150 cells treated with 30 mg/l ART were similar to those of the SHEE normal human esophageal epithelial cell line. In conclusion, the present study demonstrated that ART may inhibit cell proliferation and migration in ESCC through changes in the biomechanical properties of the ESCC cells.