Improved anti-tumor therapy based upon infectivity-enhanced adenoviral delivery of RNA interference in ovarian carcinoma cell lines

Numnum, T. Michael; Makhija, Sonia K.; Lu, Baogen; Wang, Minghui; Rivera, Angel A.; Stoff-Khalili, Mariam A.; Alvarez, Ronald D.; Zhu, Zeng B.; Curiel, David T.

doi:10.1016/j.ygyno.2007.08.096

Cited by 14 publications

(6 citation statements)

References 29 publications

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“…Dysregulation of Ndc80-NUF2 has been employed in the development of a series of human cancers, including lung cancer, colorectal cancer, gastric cancer, prostate cancer, urinary bladder cancer, renal carcinoma and ovarian cancer, rather than other normal tissues except testis [ 13 – 18 ]. It has been found that depletion of NUF2 by specific siRNAs (small interfering RNAs) resulted in inhibition of cell proliferation and induction of apoptosis in non-small-cell carcinoma and ovarian cancer [ 17 , 18 ]. Likewise, in colorectal and gastric cancers, after the siRNA-mediated knockdown against NUF2, cell growths were significantly suppressed, and subG1 fractions of cell cycle were significantly increased [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

siRNA-mediated knockdown against NUF2 suppresses pancreatic cancer proliferation in vitro and in vivo

Chen

Sun

et al. 2015

Bioscience Reports

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NUF2 (NUF2, Ndc80 kinetochore complex component) plays an important role in kinetochore-microtubule attachment. It has been reported that NUF2 is associated with multiple human cancers. However, the functional role of NUF2 in pancreatic cancer remains unclear. In this study, we found that NUF2 expression was stronger in tumour tissues than in normal pancreatic tissues, and its overexpression could be related to poor prognosis. Moreover, NUF2 was highly expressed in several human pancreatic cancer cell lines. We took advantage of lentivirus-mediated siRNA (small interfering RNA) to suppress NUF2 expression in PANC-1 and Sw1990 cell lines aiming to investigate the role of NUF2 in pancreatic cancer. NUF2 silencing by RANi (RNA interference) reduced the proliferation and colony formation ability of pancreatic cancer cells in vitro. Cell cycle analysis showed that NUF2 knockdown induced cell cycle arrest at G0/G1 phase via suppression of Cyclin B1, Cdc2 and Cdc25A. More importantly, NUF2 silencing was able to alleviate in vivo tumourigenesis in pancreatic cancer xenograft nude mice. Collectively, the present study indicates that the siRNA-mediated knockdown against NUF2 may be a promising therapeutic method for the treatment of pancreatic cancer.

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Section: Introductionmentioning

confidence: 99%

siRNA-mediated knockdown against NUF2 suppresses pancreatic cancer proliferation in vitro and in vivo

Chen

Sun

et al. 2015

Bioscience Reports

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“…One study reported that knockdown of NUF2 suppressed pancreatic cancer proliferation in vitro and in vivo [ 18 ]. Except for the testis, dysregulation of NUF2 has been reported in the development of several human cancers, including lung cancer, colorectal cancer, prostate cancer, as compared to normal tissue [ 31 , 32 ]. Depletion of NUF2 resulted in the inhibition of cell proliferation in non-small-cell carcinoma and ovarian cancer [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-3613-3p affects cell proliferation and cell cycle in hepatocellular carcinoma

et al. 2017

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Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with poor sensitivity to chemotherapy drugs and poor prognosis among patients. In the present study, we downloaded the original data from the Gene Expression Omnibus and compared gene expression profiles of liver cancer cells in patients with HCC with those of colon epithelial cells of healthy controls to identify differentially expressed genes (DEGs). After filtering target microRNAs (miRNA) from core DEGs, we cultured HepG2 cells in vitro, knocked down the miRNA and core mRNAs, and analyzed the effects. We found 228 differentially expressed genes between liver cancer tissue and healthy control tissue. We also integrated the protein-proteininteraction network and module analysis to screen 13 core genes, consisting of 12 up-regulated genes and 1 down-regulated gene. Five core genes were regulated hsa-miR-3613-3p, therefor we hypothesized that hsa-miR-3613-3p was a critical miRNA. After the transfection procedure, we found that changes in hsa-miR-3613-3p were the most obvious. Therefore, we speculated that hsa-miR-3613-3p was a main target miRNA. In addition, we transfected with si (BIRC5, CDK1, NUF2, ZWINT and SPC24), to target genes that can be targeted by miR-3613-3p. Our data shows that BIRC5, NUF2, and SPC24 may be promising liver cancer biomarkers that may not only predict disease occurrence but also potential personalized treatment options.

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“…8,18 Systemic delivery systems such as retrovirus or adenovirus can target tumor cells well, but are limited to research use in animal models due to human safety issues. 19,20 Certain bacteria have great potential as siRNA delivery vectors and have already been employed in animals and humans. 21 – 23 S. Typhimurium is an intracellular bacterial pathogen that mainly invades mucosa-associated lymphoid tissue through M cells in the intestinal mucosa and is phagocytized by macrophages and dendritic cells, in which the bacteria can proliferate.…”

Section: Discussionmentioning

confidence: 99%

Targeted therapy via oral administration of attenuated Salmonella expression plasmid-vectored Stat3-shRNA cures orthotopically transplanted mouse HCC

et al. 2012

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The development of RNA interference-based cancer gene therapies has been delayed due to the lack of effective tumor-targeting delivery systems. Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) has a natural tropism for solid tumors. We report here the use of attenuated S. Typhimurium as a vector to deliver shRNA directly into tumor cells. Constitutively activated signal transducer and activator of transcription 3 (Stat3) is a key transcription factor involved in both hepatocellular carcinoma (HCC) growth and metastasis. In this study, attenuated S. Typhimurium was capable of delivering shRNA-expressing vectors to the targeted cancer cells and inducing RNA interference in vivo. More importantly, a single oral dose of attenuated S. Typhimurium carrying shRNA-expressing vectors targeting Stat3 induced remarkably delayed and reduced HCC (in 70% of mice). Cancer in these cured mice did not recur over 2 years following treatment. These data demonstrated that RNA interference combined with Salmonella as a delivery system may offer a novel clinical approach for cancer gene therapy.

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Improved anti-tumor therapy based upon infectivity-enhanced adenoviral delivery of RNA interference in ovarian carcinoma cell lines

Cited by 14 publications

References 29 publications

siRNA-mediated knockdown against NUF2 suppresses pancreatic cancer proliferation in vitro and in vivo

siRNA-mediated knockdown against NUF2 suppresses pancreatic cancer proliferation in vitro and in vivo

MiR-3613-3p affects cell proliferation and cell cycle in hepatocellular carcinoma

Targeted therapy via oral administration of attenuated Salmonella expression plasmid-vectored Stat3-shRNA cures orthotopically transplanted mouse HCC

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