Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia

Abstract

The prognosis of chemoresistant acute myeloid leukemia (AML) is still poor, mainly owing to the sustained proliferation ability of leukemic cells, while the microtubules have a major role in sustaining the continuity of cell cycle. In the present study, we have identified CENPE, a microtubular kinesin-like motor protein that is highly expressed in the peripheral blood of patients with chemoresistant AML. In our in vitro studies, knockdown of CENPE expression resulted in the suppression of proliferation of myeloid leukemia cells and reversal of cytarabine (Ara-C) chemoresistance. Furthermore, Lin28A, one of the RNA-binding oncogene proteins that increase cell proliferation and invasion and contribute to unfavorable treatment responses in certain malignancies, was found to be remarkably correlated with CENPE expression in chemoresistance AML. Overexpression of LIN28A promoted the proliferation and Ara-C chemoresistance of leukemic cells. RIP assay, RNA pull-down, and dual luciferase reporter analyses indicated that LIN28A bound specifically to the promoter region GGAGA of CENPE. In addition, the impacts of LIN28A on cell growth, apoptosis, cell cycle progression, and Ara-C chemoresistance were reverted by the knockdown of CENPE. Hence, Lin28A/CENPE has enhanced the proliferation and chemoresistance of AML, and therefore, it could be a prospective candidate for AML treatment.

Vimentin‐positive invasive breast carcinoma of no special type: A breast carcinoma with lethal biological characteristics

“…[37][38][39] Thirteen GO terms consisted of many important coding RNAs that could play very important roles in heightening the malignant potential of vimentin-positive IBC-NSTs; among these, the 12 coding RNAs that were significantly upregulated in three or more GO terms may be especially important coding RNAs (Table 4). [40][41][42][43][44][45][46][47][48][49][50][51] This study clearly demonstrated a higher Ki67 labeling index of vimentin-positive IBC-NSTs than that of vimentin-negative IBC-NSTs; since all of the 12 coding RNAs play important roles in…”

“…Thirteen GO terms consisted of many important coding RNAs that could play very important roles in heightening the malignant potential of vimentin‐positive IBC‐NSTs; among these, the 12 coding RNAs that were significantly upregulated in three or more GO terms may be especially important coding RNAs (Table 4). 40–51 This study clearly demonstrated a higher Ki67 labeling index of vimentin‐positive IBC‐NSTs than that of vimentin‐negative IBC‐NSTs; since all of the 12 coding RNAs play important roles in cell cycle and proliferative activity of carcinoma cells, upregulation of these coding RNAs probably plays a principal role in increasing the Ki67 labeling index of vimentin‐positive IBC‐NSTs and heightening the malignant potential of vimentin‐positive IBC‐NSTs. In addition, since upregulation of TTK and RSP3 significantly accelerates protein phosphorylation and cytoplasmic translation of RNA into protein, respectively, other coding RNAs involved in protein autophosphorylation, for example, MAP3K21, YES1 , and in cytoplasmic translation, for example, RSP12, RSP7 , probably also play important roles in heightening the malignant potential of vimentin‐positive IBC‐NSTs 52–55 …”

The platelet-related genes associated with the prognosis of HCC by regulating cycling T cell and prolif-TAMs

“…The patients from subtype 1 and a high-risk group showed poor prognosis, higher mutation, and tumor mutation burden. It is worth noting that Centrosome-associated protein E (CENPE), a kinetochore protein, was involved in the progression of various tumors [ 29 , 30 ]. Epidermal growth factor (EGF) could be released by platelets, contributing to wound healing [ 31 , 32 ] and tumor growth [ 33 ].…”

CENPE and LDHA were potential prognostic biomarkers of chromophobe renal cell carcinoma

“…As a mitotic cell cycle-associated gene, CENPE has an essential and positive function in the process of mitotic cytoplasmic separation, which was related to the cell cycle [ 9 , 23 ], and the rapid proliferation is a common characteristic of tumor cells [ 24 , 25 ]. Shi et al certificated that the silencing CENPE led to the inhibition of cell proliferation and promotion of apoptosis in acute myeloid leukemia cells [ 26 ]. In addition, Wang et al found that overexpressing CENPE promoted the cell viability, migration, and invasion of neuroblastoma [ 27 ].…”