Lentivirus‐Mediated RNAi Knockdown of NUPR1 Inhibits Human Nonsmall Cell Lung Cancer Growth In Vitro and In Vivo

Abstract

NUPR1 (nuclear protein 1) was found to play a key role in the development of several malignancies including pancreas, breast, and prostate cancers. However, the functional role of NUPR1 in nonsmall cell lung cancer (NSCLC) progression and development is little known. Here, lentivirus-mediated small interfering RNA (siRNA) was employed to downregulate endogenous NUPR1 expression to study the function of NUPR1 in growth of nonsmall cell lung cancer. A lentivirus-mediated RNAi technology was used to specifically knock down the expression of NUPR1 in H1299 cells. Quantitative real-time reverse transcriptase polymerase chain reaction, flow cytometry, western blot and cell count assays were studied to characterize NUPR1 expression in vitro. Furthermore, nonsmall cell lung cancer xenograft models in nude mice were established to investigate whether knockdown of NUPR1 reduces the tumor growth in vivo. We found that downregulation of NUPR1 expression significantly inhibited nonsmall cell lung cancer H1299 cells proliferation and colony formation in vitro. Moreover, the specific downregulation of NUPR1 arrested cells in G0 phase of cell cycle and increased apoptosis rate. Silencing of NUPR1 also suppressed tumor growth by tail vein injection of lentivirus encoded shRNA against NUPR1 in vivo. Our findings revealed that the NUPR1 gene represents a promising target for gene silencing therapy in nonsmall cell lung cancer. Anat Rec, 295:2114Rec, 295: -2121Rec, 295: , 2012. V C 2012 Wiley Periodicals, Inc.

Alu- and 7SL RNA Analogues Suppress MCF-7 Cell Viability through Modulating the Transcription of Endoplasmic Reticulum Stress Response Genes

“…It is known that the expression of the transcriptional regulator gene NUPR1 (encodes protein p8) is enhanced in response to various stress factors and results in cell resistance to chemotherapeutic agents, while a decrease in NUPR1 expression is accompanied by a suppression of cancer cell growth in vitro and in vivo [33, 34]. However, an increase in the level of NUPR1 mRN A also accompanies apoptotic changes in cancer cells [35].…”

Activation of endoplasmic reticulum stress is involved in the activity of icariin against human lung adenocarcinoma cells

“…Non-small cell lung cancer (NSCLC) subtypes (adenocarcinoma, squamous cell carcinoma and large cellcarcinoma) account for 80-85 % of all lung cancers. The majority of patients diagnosed with NSCLC are diagnosed with advanced stages and have inoperable local or distant metastases [2,3]. Thus, the lung cancer treatments address major unmet needs and can most likely be improved by a better understanding of the molecular origins and evolution of the disease to decrease the incidence and severity associated with this cancer, specifically chemo-preventative agents that are generated from less harmful natural materials.…”

Genetic inactivation of the pancreatitis-inducible gene Nupr1 impairs PanIN formation by modulating KrasG12D-induced senescence

“…In this regard, the expression of genes that are targets for regulation by Nupr1 has been implicated in key protumorigenic pathways, including cell cycle regulation, matrix remodeling, autophagy, cell cannibalism and apoptosis inhibition. 9, 10, 11, 12, 13, 14, 15, 16 Moreover, the fundamental role that Nupr1 has in pancreatic tumorigenesis is underscorded by recent results, which showed that, in mice, the oncogenic form of Kras G12D is unable to promote PanINs in the absence of this chromatin protein, 17 although the mechanisms responsible for this effect remain an area of active investigation. Consequently, we designed the current study with the aim of testing the hypothesis that Nupr1 cooperates with oncogenic Kras to induce PanIN formation by modulating the expression of gene networks that are necessary for bypassing senescence.…”