Details

Autor(en) / Beteiligte

• Tsang, Wing Pui
• Ng, Enders K.O.
• Ng, Simon S.M.
• Jin, Hongchuan
• Yu, Jun
• Sung, Joseph J.Y.
• Kwok, Tim Tak

Titel

Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer

Ist Teil von

• Carcinogenesis (New York), 2010-03, Vol.31 (3), p.350-358

Ort / Verlag

Oxford: Oxford University Press

Erscheinungsjahr

2010

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• H19 is an imprinted oncofetal non-coding RNA recently shown to be the precursor of miR-675. The pathophysiological roles of H19 and its mature product miR-675 to carcinogenesis have, however, not been defined. By quantitative reverse transcription–polymerase chain reaction, both H19 and miR-675 were found to be upregulated in human colon cancer cell lines and primary human colorectal cancer (CRC) tissues compared with adjacent non-cancerous tissues. Subsequently, the tumor suppressor retinoblastoma (RB) was confirmed to be a direct target of miR-675 as the microRNA suppressed the activity of the luciferase reporter carrying the 3′-untranslated region of RB messenger RNA that contains the miR-675-binding site. Suppression of miR-675 by transfection with anti-miR-675 increased RB expression and at the same time, decreased cell growth and soft agar colony formation in human colon cancer cells. Reciprocally, enhanced miR-675 expression by transfection with miR-675 precursor decreased RB expression, increased tumor cell growth and soft agar colony formation. Moreover, the inverse relationship between the expressions of RB and H19/miR-675 was also revealed in human CRC tissues and colon cancer cell lines. Our findings demonstrate that H19-derived miR-675, through downregulation of its target RB, regulates the CRC development and thus may serve as a potential target for CRC therapy.