CBLL1 is highly expressed in non‐small cell lung cancer and promotes cell proliferation and invasion

Abstract

Background Studies have shown that E3 ubiquitin ligase CBLL1 plays multiple roles in development and tumorigenesis. CBLL1 is over‐expressed in colon cancer and associated with cancer cell proliferation. While, the overexpression of CBLL1 inhibited the estrogenic dependent cell proliferation and migration in ER alpha dependent breast cancer cell MCF‐7. Methods We used an immunohistochemical method to detect CBLL1 expression in human NSCLC and corresponding normal lung tissues and analyzed its relationship with clinicopathological parameters. Moreover, we investigated the role of CBLL1 in NSCLC cell behavior by inhibiting its expression in A549 and H1299 cells. Results In this study, we found that CBLL1 was frequently upregulated in non‐small lung cancer (NSCLC) tissues compared to the adjacent nontumor tissues. We found that the high expression of CBLL1 was associated with the tumor size in NSCLC tissues. It has been recently reported that CBLL1 promotes cell proliferation and invasion in A549 and H460 cells. Our results confirmed that CBLL1 promoted the proliferation by promoting G1/S cell cycle transition in NSCLCs cells. Moreover, CBLL1 knockdown inhibited cell invasion via increased E‐cadherin protein expression, and decreased expression of MMP2 and MMP9 in NSCLC cell lines. The protein expression of E‐cadherin was increased after CBLL1 depletion while the E‐cadherin mRNA was not affected after knockdown of the endogenous CBLL1. Conclusion These results provide important insights for using CBLL1 as an oncogenic marker gene in the development and progression of non‐small cell lung cancer.

Circ_0072083 interference enhances growth-inhibiting effects of cisplatin in non-small-cell lung cancer cells via miR-545-3p/CBLL1 axis

“…Next, CBLL1 was predicted and confirmed as a target of miR-545-3p through Targetscan software and dual-luciferase reporter assay, respectively. CBLL1 was up-regulated in NSCLC and breast cancer [18,19,30]. Consistent with the previous studies, we found that the expression of CBLL1 was elevated in NSCLC tissues and cells.…”

“…Accumulating articles have reported the role of CBLL1 in NSCLC. Hui et al found that the expression of CBLL1 was higher in NSCLC, and it facilitated the growth and motility of NSCLC cells [18]. Qui et al reported that XIST accelerated the proliferation and metastasis of NSCLC cells via acting as a miR-212-3p sponge and up-regulating CBLL1 [19].…”

Heat Shock Protein 90 Chaperone Regulates the E3 Ubiquitin-Ligase Hakai Protein Stability

“…HSP90 is required for the stability and function of numerous oncogenic proteins, and its specific inhibitors display multiple anticancer effects [30][31][32]. On the other hand, Hakai is considered an oncogenic protein that was reported to be overexpressed in various cancers such as colon and lung cancer [16,19,20], furthermore, Hakai knockdown inhibits cell migration [33]. Therefore, we decided to test whether Hsp90 geldanamycin inhibitor may indeed influence the migratory effect driven by Hakai.…”

The Role of CBLL1 in the Prognosis and Immune Infiltration of Pan-Cancer

“…The overexpression of CBLL1 promotes the cell cycle transition of G1-S, which leads to cell proliferation and invasion. Interfering with the expression of CBLL1 gene inhibits cell invasion by increasing the expression of adhesion proteins, and reduces the expression of MMP2 and MMP9 in cells [2,3]. Compared with healthy human colon tissue, Hakai is highly expressed in adenoma and colon adenocarcinoma, and is related to patient stage.…”