p73-regulated FER1L4 lncRNA sponges the oncogenic potential of miR-1273g-3p and aids in the suppression of colorectal cancer metastasis

Apoorva Uboveja; Yatendra Kumar Satija; Fouzia Siraj; Daman Saluja

doi:10.1016/j.isci.2022.103811

p73-regulated FER1L4 lncRNA sponges the oncogenic potential of miR-1273g-3p and aids in the suppression of colorectal cancer metastasis

iScience. 2022 Jan 29;25(2):103811. doi: 10.1016/j.isci.2022.103811. eCollection 2022 Feb 18.

Authors

Apoorva Uboveja¹, Yatendra Kumar Satija¹, Fouzia Siraj², Daman Saluja¹

Affiliations

¹ Dr.B.R. Ambedkar Centre for Biomedical Research and Delhi School of Public Health, University of Delhi, New Delhi 110007, India.
² National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi 110029, India.

Abstract

p73 belongs to the p53 tumor suppressor family and is involved in the suppression of metastasis. However, its specific mechanism of action remains to be elucidated. Long non-coding RNAs portray a crucial role in tumor suppression. We have identified lncRNA FER1L4 as a p73 transcriptional target. The binding of p73 to FER1L4 promoter was established by bioinformatics analysis, luciferase reporter, and ChIP assays. Both FER1L4 and p73 knockdown enhanced the migration and invasion rate of colorectal cancer cells. FER1L4 also plays a critical role in p73-mediated cell-cycle arrest and apoptosis. FER1L4 sponged the expression of miR-1273g-3p, which, in turn, increased PTEN expression, leading to cell-cycle arrest. RNA in situ hybridization revealed the down-regulation of both p73 and FER1L4 expression in a metastatic colon cancer tissue as compared with non-metastatic tissue. Collectively, we impart conclusive proof that p73 exerts its anti-metastatic properties by inducing lncRNA FER1L4 in response to genotoxic stress.

Keywords: Cancer; Cell biology; Molecular biology.