Hic-5 in pancreatic stellate cells affects proliferation, apoptosis, migration, invasion of pancreatic cancer cells and postoperative survival time of pancreatic cancer

Qian, Bo; Wei, Liping; Yang, Zhongqiu; He, Qinyuan; Chen, Hao; Wang, Ankang; Yang, Dayin; Li, Qiu; Li, Jing; Zheng, Silin; Fu, Wenguang

doi:10.1016/j.biopha.2019.109355

Cited by 15 publications

(11 citation statements)

References 44 publications

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“…Apoptosis, known as programmed cell death, suppressescarcinogenesis in normal cells by regulating expression of cancer-related genes [ 23 ]. As an anti-apoptotic protein, Mcl-1 belongs to the BCL-2 family, which is closely connected to inhibitions of mitochondrial apoptosis [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

LiCl induces apoptosis via CHOP/NOXA/Mcl-1 axis in human choroidal melanoma cells

Zhang

et al. 2021

Cancer Cell Int

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Background Choroidal melanoma is the most common primary intraocular malignancy that occurs in adults. Lithium Chloride Promotes Apoptosis in Human Leukemia NB4 Cells by Inhibiting Glycogen Synthase Kinase-3 Beta. In this study, we aimed to understand whether LiCl exerts anticancer effects on choroidal melanoma cells and elucidate the underlying molecular mechanisms. Methods Human choroidal melanoma cells were treated with LiCl, and cell survival was assessed with MTT assays. Cell reproductive viability was measured by plate colony formation assays. Cell apoptosis was evaluated using flow cytometry, and proteins were detected using western blotting. A human choroidal melanoma xenograft model was established to demonstrate the effect of LiCl on human choroidal melanoma in vivo. Results We found that LiCl inhibited cell survival and clonogenic potential and induced apoptosis in human choroidal melanoma cells. LiCl also reduced the proliferation of choroidal melanoma cells in vivo. Moreover, the upregulation of NOXA and downregulation of Mcl-1 were responsible for LiCl-induced apoptosis. Mcl-1 overexpression obviously impaired LiCl-induced apoptosis and cleavage of caspase8, caspase9, caspase3 and PARP. Moreover, the protein expression of endoplasmic reticulum stress markers, including IRE1α, Bip, p-eIF2α, ATF4 and CHOP, were upregulated following treatment with LiCl. When CHOP expression was knocked down and cells were treated with LiCl, the protein level of NOXA was partially increased, and Mcl-1 expression was increased, while the cleavage of caspase8, caspase9, caspase3 and PARP that was induced by the LiCl was reduced compared with the vehicle treated group. Prolonged ER stress results in the activation of the apoptotic pathway. Conclusions In summary, LiCl induced an endoplasmic reticulum stress response while activating intrinsic apoptosis. Furthermore, the CHOP/NOXA/Mcl-1 axis contributed to LiCl-induced apoptosis both in vitro and in vivo. The present study provides important mechanistic insight into potential cancer treatments involving LiCl and enhances the understanding of human choroidal melanoma.

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Section: Discussionmentioning

confidence: 99%

LiCl induces apoptosis via CHOP/NOXA/Mcl-1 axis in human choroidal melanoma cells

Zhang

et al. 2021

Cancer Cell Int

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“…PDAC is characterized by aggressive migration and invasion (18,19). The increased pseudopods caused the aggressive movement of cancer cells.…”

Section: N2e4 Affects the Formation Of Pseudopods And The E-cadherin/ N-cadherin Switch In Emtmentioning

confidence: 99%

N2E4, a Monoclonal Antibody Targeting Neuropilin-2, Inhibits Tumor Growth and Metastasis in Pancreatic Ductal Adenocarcinoma via Suppressing FAK/Erk/HIF-1α Signaling

Wang

et al. 2021

Front. Oncol.

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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with extremely limited treatment; the effective targeting strategy stays an urgent unmet need. Neuropilin-2 (NRP2), a multifunctional transmembrane non-tyrosine-kinase glycoprotein, enhances various signal transduction pathways to modulate cancer progression. However, the application value of NRP2 as a therapeutic target in pancreatic cancer is still unclear. Here, we detected the elevated NRP2 was associated with the poor prognosis of pancreas carcinoma. The mouse monoclonal antibody targeting NRP2 (N2E4) that could specifically bind to PDAC cells was developed. Moreover, N2E4 inhibits PDAC proliferation, migration, and invasion in vitro, and repressed growth and metastasis in vivo. Mechanistically, the effect of N2E4 was mainly related to the blocking of interaction between NRP2 with integrinβ1 to inhibit FAK/Erk/HIF-1a/VEGF signaling. Therefore, N2E4 has the potential for targeting therapy of PDAC. This study lays a foundation for the future development of NRP2-based targeted therapy for PDAC.

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“…However, for the majority of patients with PAAD, surgery is not a viable option due to a high chance of a relapse occurring ( 23 , 28 , 29 ). Therapeutic prospects for PAAD remain poor even with improved treatment strategies because of the high risk of metastasis ( 23 , 30 , 31 ). Due to the complicated configuration of the adjoining anatomy of the pancreas, whereby the pancreas is in contact with numerous neighboring structures, pancreatic cancer cells tend to also aggressively attack the adjacent tissues ( 24 , 25 , 30 , 32 ).…”

Section: Discussionmentioning

confidence: 99%

miR‑32‑5p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting TLDC1

et al. 2021

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Pancreatic adenocarcinoma (Paad) is one of the most fatal types of cancer in humans. However, the molecular mechanisms underlying the migration and invasion abilities of Paad cells remain unclear. The aim of the present study was to explore the regulatory roles of microrna (mir)-32-5p in Paad cells. mir-32-5p mimic and inhibitor were used to transfect the human Paad asPc-1 cell line to determine the role of mir-32-5p in cell proliferation and metastasis. The starBase database predicted the binding of mir-32-5p to the target gene TBc/lysM-associated domain containing 1 (Tldc1). Further analyses were performed to assess mir-32-5p and Tldc1 expression levels in healthy and Paad tissues, as well as the association between mir-32-5p or Tldc1 expression and the prognosis of patients with Paad. The interaction between miR-32-5p and TLDC1 was verified using the dual-luciferase reporter assay. mir-32-5p and Tldc1 expression levels were detected by reverse transcription-quantitative Pcr and western blotting, respectively. The cell counting Kit-8 assay was utilised to assess cell proliferation, whereas the wound-healing and Transwell assays were conducted to assess cell migration and invasion, respectively. mir-32-5p expression levels were markedly lower in Paad tissue compared with those in healthy tissue, and were significantly lower in Paad cell lines compared with those in the human pancreatic duct cell line HPde6, which corresponded with poor prognosis. miR-32-5p significantly inhibited the proliferation of Paad cells and markedly reduced migration and invasion compared with the negative controls. mir-32-5p was shown to target Tldc1, with mir-32-5p expression in Paad being negatively correlated with Tldc1 expression. High Tldc1 expression levels were associated with a poorer prognosis compared with low Tldc1 expression levels. co-transfection of mir-32-5p mimic and pcdna/Tldc1 demonstrated that TLDC1 significantly reversed miR-32-5p-mediated inhibition of the proliferation, migration and invasion of Paad cells. overall, the present study demonstrated that mir-32-5p may serve as a tumor-suppressor gene by inhibiting the proliferation and migration and invasion of Paad cells via the downregulation of Tldc1. Therefore, mir-32-5p may serve as a potential diagnostic or prognostic marker for Paad.

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Hic-5 in pancreatic stellate cells affects proliferation, apoptosis, migration, invasion of pancreatic cancer cells and postoperative survival time of pancreatic cancer

Cited by 15 publications

References 44 publications

LiCl induces apoptosis via CHOP/NOXA/Mcl-1 axis in human choroidal melanoma cells

LiCl induces apoptosis via CHOP/NOXA/Mcl-1 axis in human choroidal melanoma cells

N2E4, a Monoclonal Antibody Targeting Neuropilin-2, Inhibits Tumor Growth and Metastasis in Pancreatic Ductal Adenocarcinoma via Suppressing FAK/Erk/HIF-1α Signaling

miR‑32‑5p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting TLDC1

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