NUCKS1 promotes the progression of colorectal cancer via activating PI3K/AKT/mTOR signaling pathway

Abstract

Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) is highly expressed in a variety of malignant tumors and functions as an oncogene; however, its role in colorectal cancer (CRC) remains unclear. We aimed to explore the function and regulatory mechanisms of NUCKS1 and potential therapeutic agents targeting NUCKS1 in CRC. We knocked down and overexpressed NUCKS1 in CRC cells and explored its e ects in vitro and in vivo. Flow cytometry, CCK-8, Western blotting, colony formation, immunohistochemistry, in vivo tumorigenic, and transmission electron microscopy analyses were performed to determine the e ects of NUCKS1 on CRC cell function. LY294002 was used to examine the mechanism of NUCKS1 expression in CRC cells. Potential therapeutic agents for NUCKS1-high CRC patients were analyzed using the CTRP and PRISM datasets, and the function of selected agents was determined by CCK-8 and Western blotting. We revealed that NUCKS1 was highly expressed in CRC tissues and clinically correlated with poor prognosis in CRC patients. NUCKS1 knockdown induces cell cycle arrest, inhibits CRC cell proliferation, and promotes apoptosis and autophagy. ese results were reversed when NUCKS1 was overexpressed. Mechanistically, NUCKS1 exerts a cancer-promoting function by activating the PI3K/AKT/mTOR signaling pathway. is was reversed when LY294002 was used to inhibit the PI3K/AKT pathway. Furthermore, we determined that mitoxantrone exhibited high drug sensitivity in NUCKS1-overexpressing CRC cells. is work demonstrated NUCKS1 plays a crucial role in CRC progression via the PI3K/AKT/mTOR signaling pathway. Additionally, mitoxantrone may be a potential therapeutic agent for CRC treatment.erefore, NUCKS1 represents a promising anti-tumor therapeutic target.

TRIM58 functions as a tumor suppressor in colorectal cancer by promoting RECQL4 ubiquitination to inhibit the AKT signaling pathway

“…Moreover, it has been reported that RECQL4 expression is increased in CRC [ 21 ] and it exacerbates resistance to oxaliplatin in colon adenocarcinoma via the activation of the PI3K/AKT signaling pathway [ 22 ]. PI3K/AKT is a classical signaling pathway that is involved in a variety of biological processes, such as regulating cellular metabolism, autophagy, cell cycle, cell proliferation, apoptosis, and metastasis [ 37 , 38 ]. Therefore, it plays a crucial role in the occurrence and development of CRC.…”

Exploring Intrinsic Disorder in Human Synucleins and Associated Proteins

“…This protein is known to bind to the double-stranded DNA (dsDNA) and also can interact with the secondary DNA structures, such as D-loop structures [266]. NUCKS1 is highly expressed in a variety of malignant tumors, such as breast cancer [267,268], hepatocellular carcinoma [269,270], ovarian cancer [271], gastric cancer [272], and cervical squamous cell carcinoma [273], and is believed to function as an oncogen [274]. This protein was shown to promote the progression of colorectal cancer by activating the PI3K/AKT/mTOR signaling pathway [274].…”

“…NUCKS1 is highly expressed in a variety of malignant tumors, such as breast cancer [267,268], hepatocellular carcinoma [269,270], ovarian cancer [271], gastric cancer [272], and cervical squamous cell carcinoma [273], and is believed to function as an oncogen [274]. This protein was shown to promote the progression of colorectal cancer by activating the PI3K/AKT/mTOR signaling pathway [274]. In osteosarcoma, NUCKS1 elevates asparagine synthesis by transcriptionally upregulating asparagine synthetase (ASNS) expression, thereby promoting osteosarcoma progression and metastasis [275].…”

Tumor-related factor complement Clq/TNF-related protein 6 affects the development of digestive system tumors through the phosphatidylinositol 3-kinase pathway

“…CTRP6's role in tumorigenesis is multifaceted, with evidence suggesting that it can both promote and inhibit tumor growth, depending on the cancer type[ 9 ]. In the context of digestive system tumors, such as gastric and liver cancers, CTRP6 has been shown to be overexpressed and is implicated in tumor cell proliferation, migration, and angiogenesis[ 10 ].…”