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miR-144 reverses cisplatin resistance in cervical cancer via targeting LHX2
Authors:Fan Shi  Jin Su  Zi Liu  Jiquan Wang  Tao Wang
Institution:Department of Radiation Oncology, First Hospital of Xi'an Jiaotong Univesity, Xi'an, Shaanxi, China
Abstract:Mounting evidence showed that microRNAs involve in development and chemoresistance of various human cancers. We explored the roles and mechanisms of miR-144 in resistance to cisplatin (CDDP) of cervical cancer cells. miR-144 and LIM homeobox 2 (LHX2) expression in CDDP-resistant and the parental cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. The functions of miR-144 overexpression on cell viability, the incidence of apoptosis, the activity of caspase-3/7, the cleaved-caspase-3 expression, cell migration, and invasion were determined in Hela cells and Hela/CDDP cells. Overexpression of miR-144 reduced cell viability, induced cell apoptosis, and inhibited cell migration and invasion after CDDP treatment. Besides, a luciferase reporter system demonstrated that miR-144 could directly bind to the 3′ untranslated region (3′-UTR) of LHX2 messenger RNA (mRNA). Gain expression of miR-144 decreased the expression of LHX2 both in mRNA and protein levels. Furthermore, restoration of LHX2 partly abolished the biological functions of miR-144 in resistance of cervical cancer cells. Taken together, miR-144 overcomes resistance to CDDP via promoting cell apoptosis and inhibiting invasion through targeting LHX2 in cervical cancer cells.
Keywords:cervical cancer  cisplatin  miR-144  resistance LXH2
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