TGFβ mediated LINC00273 upregulation sponges mir200a-3p and promotes invasion and metastasis by activating ZEB1

Arnab Sarkar, Ashikur Rahaman, Ipsita Biswas, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Transforming growth factor β (TGFβ) is a prominent cytokine that promotes tumor progression by activating epithelial-to-mesenchymal transition (EMT). This study indicated that TGFβ exerted metastasis by inducing zinc finger E-box binding homeobox 1 (ZEB1) and a long noncoding RNA, LINC00273, expressions in A549 cells. Knocking down LINC00273 diminished TGFβ induced ZEB1 expression as well as metastasis. Mechanistically, LINC00273 acted as a molecular sponge of microRNA (miR)-200a-3p which liberate ZEB1 to perform its prometastatic functions. LINC00273 knockdown and miR200a3p mimic transfection of A549 cells were used for validating the link between TGFβ and LINC00273 induced metastasis. RNA pulldown and luciferase assay were performed to establish mir200a-3p-LINC00273 interaction. High expressions of LINC00273, TGFβ, and ZEB1 with concurrent low miR200a-3p expression had been verified in vivo and in patient samples. Overall, LINC00273 promoted TGFβ-induced lung cancer EMT through miR-200a-3p/ZEB1 feedback loop and may serve as a potential target for therapeutic intervention in lung cancer metastasis.

Original languageEnglish
Pages (from-to)7159-7172
Number of pages14
JournalJournal of Cellular Physiology
Volume235
Issue number10
DOIs
StatePublished - 1 Oct 2020
Externally publishedYes

Keywords

  • TGFβ
  • ZEB1
  • long noncoding RNA (lncRNA)
  • lung cancer
  • metastasis
  • miR-200a-3p

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