Knockdown of NOLC1 Inhibits PI3K-AKT Pathway to Improve the Poor Prognosis of Esophageal Carcinoma

Abstract

Objective. Esophageal carcinoma (ESCA) is a common malignant gastrointestinal tumor. The abnormal expression of NOLC1 is involved in the tumorigenesis of various human tumors, whereas the function and mechanism of NOLC1 in ESCA remain unclear. In this study, we explored the relationship between NOLC1 and poor prognosis of ESCA, and its role and mechanism in the occurrence of ESCA. Methods. The NOLC1 expression in ESCA tissues and cell lines was determined by qRT-PCR, immunohistochemistry, or western blot. The Kaplan–Meier method was conducted to estimate the overall survival. Cox regression analysis was carried out to examine the association between patient characteristics and prognosis. A recombined lentiviral vector containing NOLC1 was applied for transfecting ESCA cells (Eca109 and TE-13) and established a stable cell line with low NOLC1 expression or high NOLC1 expression, in the absence or presence of PI3K inhibitor (LY294002) treatment. Cell proliferation, apoptosis rate, invasion ability, migration ability, and PI3K/AKT pathway were detected by CCK8 assay, flow cytometry, Transwell assay, wound-healing assay, and western blot. Results. NOLC1 overexpression was observed in ESCA tissues and ESCA cell lines (EC9706, Eca109, TE-13, Kyse170, T.TN) compared with adjacent normal tissues and normal esophageal cell line HEEC. NOLC1 overexpression was markedly associated with bigger tumor size, lymph node metastasis, and advanced TNM stage. Patients with NOLC1 overexpression have shorter overall survival than that of those with low NOLC1 expression. NOLC1 overexpression was considered to be an independent poor prognostic factor affecting overall survival. NOLC1 knockdown inhibited proliferation, migration, invasion, and cyclin B1 expression and promoted the apoptosis and cleaved-caspase-3 expression of Eca109 and TE-13 cells. NOLC1 overexpression accelerated proliferation, migration, invasion, and cyclin B1 expression and inhibited the apoptosis and cleaved-caspase-3 expression of ESCA cells via activating PI3K/AKT pathway. Rescue experiments showed that PI3K inhibitor (LY294002) could reverse the phenomenon caused by NOLC1 overexpression. Conclusion. NOLC1 may be a marker for poor prognosis. It can participate in the occurrence and development of ESCA via the PI3K/AKT pathway.

High expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer

“…Fuwen Yuan et al also found that highly expressed NOLC1 promotes cell senescence and inhibits cell proliferation in HCC and plays a certain role in cell senescence through the CSIG–NOLC1–RRNA pathway (Yuan et al 2017 ). Kong et al ( 2021 ) also reported that NOLC1 over-expression is considered to be an independent adverse factor affecting the overall survival of esophageal cancer patients and can participate in the invasion and protein expression of esophageal cancer through the PI3K/AKT pathway. However, the significance of NOLC1 expression in the prognosis of colorectal cancer remains unclear.…”

A Shortcut from Genome to Drug: The Employment of Bioinformatic Tools to Find New Targets for Gastric Cancer Treatment

“…In a study carried out by Kong et al [ 47 ], the role of NOLC1 in esophageal cancer (ESCA) was determined, and its gene expression in ESCA tissues and cell lines was evaluated by qRT-PCR, immunohistochemistry or Western blotting. Among the results, overexpression of NOLC1 was observed in ESCA tissues and ESCA cell lines (EC9706, Eca109, TE-13, Kyse170, T.TN) compared to adjacent normal tissues and normal esophageal cell lines.…”

“…So, NOLC1 overexpression was also associated with reduced overall survival rates for patients with ESCA. NOLC1 knockdown, in turn, inhibited proliferation, migration, invasion and cyclin B1 expression and promoted apoptosis and cleaved-caspase-3 expression of two ESCA cell lines [ 47 ]. The in-depth study of data on NOLC1 gene expression and its role in carcinogenesis shows that the protein encoded by this gene is a promising therapeutic target.…”

“…Cell life is a result of the interaction and coordinated activity of many proteins working at the same time. Different proteins from different pathways work together to provide a meaningful biological process essential to cell development [ 47 , 48 , 49 ]. In cancer, protein–protein interaction is essential to form complexes, allowing uncontrolled cellular division, development, growth and tumor promotion.…”

The Construction and Analysis of ceRNA Network in H pylori infection atrophic gastritis

“…It also promotes the proliferation and malignant transformation of tumor cells through phosphorylation of PI3K and AKT protein and inhibits the apoptosis of tumor cells. More and more studies have reported that PI3K/AKT signaling pathway regulates the growth, apoptosis and invasion of tumor cells in malignant tumors of digestive system [27] .Previous studies p-PI3K can activate Akt to form p-Akt, and then participate in the process of gastric cancer development and development [28,29,30,31,32] .ZHANG et al [33] validated that YARS exerted its malignant roles in GC through activated PI3K-Akt signaling.KONG et al's [34] experiments showed that NOLC1 overexpression accelerated proliferation, migration, invasion, and cyclin B1 expression and inhibited the apoptosis and cleaved-caspase-3 expression of Esophageal carcinoma (ESCA) cells via activating PI3K/AKT pathway. CHENG et al [35] found blockage of Osteopontin (OPN) downregulates the activation of the PI3K-AKT-GSK/3b-b/catenin pathway, accompanied by the inhibition of CRC stem cell proportion.…”