LINCRNA00273 promotes cancer metastasis and its G-Quadruplex promoter can serve as a novel target to inhibit cancer invasiveness
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Samarjit Jana2,*, Jagannath Jana1,*, Kartick Patra2, Soma Mondal1, Jyotsna Bhat1, Arnab Sarkar2, Pallabi Sengupta1, Anindya Biswas3, Meghomukta Mukherjee1, Satya Prakash Tripathi5, Rahul Gangwal5, Joyita Hazra6, Abhay T. Sangamwar7 Gopeswar Mukherjee4, Shamee Bhattacharjee2, Deba Prasad Mandal2 and Subhrangsu Chatterjee1
1Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VIIM, Kankurgachi, Kolkata 700054, India
2Department of Zoology, West Bengal State University, Malikapur, Kolkata 700126, India
3Department of Biochemistry, Bose Institute, P-1/12 CIT Scheme VIIM, Kankurgachi, Kolkata 700054, India
4Barasat Cancer Research and Welfare Centre, Barasat, Kolkata 700124, India
5Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S. A. S. Nagar, Punjab 160062, India
6Department of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme VIIM, Kankurgachi Kolkata 700054, India
7Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S. A. S. Nagar, Punjab 160062, India
*These authors have contributed equally to this work
Subhrangsu Chatterjee, email: [email protected]
Deba Prasad Mandal, email: [email protected]
Shamee Bhattacharjee, email: [email protected]
Keywords: long non coding intergenic RNA; cancer metastasis; G-quadruplex; epithelial to mesenchymal transition
Received: September 20, 2016 Accepted: September 13, 2017 Published: November 17, 2017
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-β’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.
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