Oncogenic role of abnormal spindle‑like microcephaly‑associated protein in lung adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is a common malignant cancer worldwide. It is urgent to explore its underlying molecular mechanism and identify novel diagnostic biomarkers. Abnormal spindle-like microcephaly (ASPM) has recently received considerable attention due to its function in tumor progression. However, its role in LUAD is unclear. The present study aimed to explore the clinical role of ASPM in LUAD. Seven pairs of LUAD and adjacent normal tissues were collected to identify potential LUAD biomarkers using transcriptome sequencing. The association between ASPM expression and LUAD progression was evaluated using bioinformatics analysis and data obtained from clinical specimens. Using small interfering RNA technology, the function of ASPM was analyzed in the LUAD H1299 and A549 cell lines. Transcriptional profiling of ASPM-deficient H1299 cells was then performed to determine the downstream targets of ASPM. Using databases and clinical specimens, it was revealed that ASPM expression was frequently elevated in LUAD tissues, and this upregulation was highly associated with LUAD progression. ASPM served as an oncogenic regulator of LUAD cell proliferation and metastasis. Mechanistically, ASPM facilitated epithelial-mesenchymal transition (EMT) via the PI3K/AKT signaling pathway and 740 Y-P, an activator of this pathway, restored the migratory ability of ASPM-knockdown LUAD cells. The current study identified ASPM as an independent prognostic biomarker of LUAD that served an important oncogenic role in regulating LUAD cell metastasis by promoting EMT via the PI3K/AKT signaling pathway. Targeting ASPM may therefore be a therapeutic strategy for treating LUAD.

Inositol monophosphatase 1 (IMPA1) promotes triple‐negative breast cancer progression through regulating mTOR pathway and EMT process

“…Deciphering signaling pathway networks is important for understanding the molecular mechanisms of IMPA function. As previously reported, KIF14 promotes the proliferation by regulating the phosphorylation of AKT, 18 and ASPM regulates lung adenocarcinoma cell metastasis by promoting epithelial‐mesenchymal transition (EMT) through the PI3K/Akt signaling pathway 19 . FAM83D is associated with EMT process 20 and regulates cancer cell proliferation and migration through Akt/mTOR pathway 21 .…”

“…As previously reported, KIF14 promotes the proliferation by regulating the phosphorylation of AKT, 18 and ASPM regulates lung adenocarcinoma cell metastasis by promoting epithelial‐mesenchymal transition (EMT) through the PI3K/Akt signaling pathway. 19 FAM83D is associated with EMT process 20 and regulates cancer cell proliferation and migration through Akt/mTOR pathway. 21 Moreover, KIF20B mediates colorectal cancer cell migration and invasion though promoting EMT process.…”

“…Overexpression of CENPF promotes the EMT process of liver cancer cells 28 . ASPM promotes the EMT process through the PI3K/AKT pathway 19 . Therefore, IMPA1 participates in mTOR pathway and promotes EMT process, at least in part, dependent on these target genes.…”

“… 28 ASPM promotes the EMT process through the PI3K/AKT pathway. 19 Therefore, IMPA1 participates in mTOR pathway and promotes EMT process, at least in part, dependent on these target genes. Together, these findings established that IMPA1 increases TNBC progression through, at least in part, upregulating those five downstream targets and their associated mTOR pathway and EMT process in TNBC cells (Figure 7 ).…”

METTL3‐mediated m6A methylation of ASPM drives hepatocellular carcinoma cells growth and metastasis

“…Recently, ASPM has been proved to participate in the cancers progression through diverse mechanisms. Wang J et al suggested that ASPM served an crucial oncogenic part in regulating LUAD cell migration by facilitating epithelial‐mesenchymal transition via the PI3K/AKT pathway, 10 and Yuan Y J et al clarified that ASPM contributed to the development of LSCC by mediating CDK4 11 . However, whether and how ASPM regulates LIHC progression remain elusive.…”