Dataset Information

LINCRNA00273 promotes cancer metastasis and its G-Quadruplex promoter can serve as a novel target to inhibit cancer invasiveness.

ABSTRACT: Discovery of anti-metastatic drugs is of immense clinical significance as metastasis is responsible for 90% of all cancer deaths. Here we report the inhibitory effect of a bis schiff base (M2) on cancer cell migration and invasion in vitro and in vivo. M2 has shown good solubility and permeability across the intestinal cell wall and hence can be classified as BCS (Biopharmaceutical classification system) class I. Microarray studies identified a long non coding intergenic RNA, LINC00273 as a novel molecular target of M2. We report that LINC00273 harbors a unique (4n-1) parallel G-Quadruplex structure in its promoter as validated by DMS footprint. M2 is proposed to stabilize this G-quadruplex structure resulting in the down-regulation of LINC00273 expression. Dual Luciferase reporter assay also suggests inhibition of LINC00273 promoter activity by M2. Involvement of this linc in metastasis is proven by siRNA and shRNA mediated knock down of LINC00273 in vitro and in vivo in nude mice which significantly decelerates cancer cell migration and invasion and also makes the cells unresponsive to TGF-?'s pro-metastatic effects. Furthermore, the real time expression of LINC00273 in thirty seven human clinical samples is found to be positively correlated with the histopathological staging of metastasis.

SUBMITTER: Jana S

PROVIDER: S-EPMC5746379 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LINCRNA00273 promotes cancer metastasis and its G-Quadruplex promoter can serve as a novel target to inhibit cancer invasiveness.

Jana Samarjit S Jana Jagannath J Patra Kartick K Mondal Soma S Bhat Jyotsna J Sarkar Arnab A Sengupta Pallabi P Biswas Anindya A Mukherjee Meghomukta M Tripathi Satya Prakash SP Gangwal Rahul R Hazra Joyita J Sangamwar Abhay T AT Mukherjee Gopeswar G Bhattacharjee Shamee S Mandal Deba Prasad DP Chatterjee Subhrangsu S

Oncotarget 20171117 66

Discovery of anti-metastatic drugs is of immense clinical significance as metastasis is responsible for 90% of all cancer deaths. Here we report the inhibitory effect of a bis schiff base (M2) on cancer cell migration and invasion <i>in vitro</i> and <i>in vivo</i>. M2 has shown good solubility and permeability across the intestinal cell wall and hence can be classified as BCS (Biopharmaceutical classification system) class I. Microarray studies identified a long non coding intergenic RNA, LINC0 ...[more]

PMID: 29299144

Similar Datasets

Project description:Invasive breast cancer (BrCa) is predicted to affect 1 in 9 women in a lifetime;1 in 32 will die from this disease. The most aggressive forms of BrCa, basal-like/triple-negative phenotype (TNBC), are challenging to treat and result in higher mortality due high number of metastatic cases. There is a paucity of options for TNBC treatment, which highlights the need for additional innovative treatment approaches. NIH-III mice were injected in the abdominal mammary fat pad with luciferase-expressing derivative of the human TNBC cell line, MDA-MB-231 cells. Animals were gavage-fed with nitrofen at the doses of 1, 3 or 6 mg/kg/alternate days. However, several structural properties/components of nitrofen raise concerns, including its high lipophilicity (cLogP of nearly 5) and a potential toxophore in the form of a nitroarene group. Therefore, we developed analogues of nitrofen which lack the nitro group and/or have replaced the diaryl ether linker with a diarylamine that could allow modulation of polarity. In vitro anti-invasiveness activity of nitrofen analogues were evaluated by quantitative determination of invasion of MDA-MB-231-Luciferase cells through Matrigel using a Boyden chamber. Our in vivo data show that nitrofen efficiently blocks TNBC tumor metastasis. In vitro data suggest that this is not due to cytotoxicity, but rather is due to impairment of invasive capacity of the cells. Further, using an in vitro model of EMT, we show that nitrofen interferes with the process of EMT and promotes mesenchymal to epithelial transformation. In addition, we show that three of the nitrofen analogues significantly reduced invasive potential of TNBC cells, which may, at least partially, be attributed to the analogues' ability to promote mesenchymal to epithelial-like transformation of TNBC cells. Our study shows that nitrofen, and more importantly its analogues, are significantly effective in limiting the invasive potential of TNBC cell lines with minimal cytotoxic effect. Further, we demonstrate that nitrofen its analogues, are very effective in reversing mesenchymal phenotype to a more epithelial-like phenotype. This may be significant for the treatment of patients with mesenchymal-TNBC tumor subtype who are well known to exhibit high resistance to chemotherapy.

Dataset Information

LINCRNA00273 promotes cancer metastasis and its G-Quadruplex promoter can serve as a novel target to inhibit cancer invasiveness.

Publications

LINCRNA00273 promotes cancer metastasis and its G-Quadruplex promoter can serve as a novel target to inhibit cancer invasiveness.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets