Abstract
Long noncoding RNA (lncRNA) highly upregulated in liver cancer (HULC) has been reported to be implicated in chemoresistance. However, the potential mechanism of HULC in paclitaxel (PTX)-resistant ovarian cancer (OC) remains undefined. The expression of RNAs and proteins was measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot assay. The PTX resistance and apoptotic rate were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Furthermore, the interaction between miR-137 and HULC or integrin beta-8 (ITGB8) was predicted by miRcode and starBase v2.0 and then verified by dual luciferase reporter and RNA pull-down assays. In addition, the xenograft mice model was established to explore the effects of HULC in vivo. HULC was significantly upregulated and miR-137 was downregulated in PTX-resistant OC tissues and cells. Also, the HULC depletion suppressed tumor growth and PTX resistance in PTX-treated mice. miR-137 was verified as a target of HULC and directly targeted ITGB8. And HULC knockdown downregulated ITGB8 expression by targeting miR-137. miR-137 inhibitor or ITGB8 overexpression mitigated the suppressive impacts of HULC knockdown on PTX resistance. Collectively, HULC modulated ITGB8 expression to promote PTX resistance of OC by sponging miR-137.
Highlights
Ovarian cancer (OC) is one of the most lethal gynecologic malignancies with poor prognosis
3.1 highly upregulated in liver cancer (HULC) expression was enhanced while miR-137 expression was decreased in PTX-resistant OC tissues and cells
Han and Ma indicated that HULC upregulated the expression of myeloid cell leukemia 1 (MCL1) by sponging miR-150-5p, thereby enhancing the resistance of CML cells to imatinib [18]
Summary
Ovarian cancer (OC) is one of the most lethal gynecologic malignancies with poor prognosis. Due to the insidious onset and indistinct symptoms as well as the lack of effective screening approaches, 70% of patients are often diagnosed in the late stages [1,2]. Surgery, chemotherapy, and radiotherapy are three main approaches for OC therapy. Paclitaxel (PTX), an antineoplastic agent, which inhibits cellular mitosis and plays a vital role in the therapy of cancer, is recommended as a typical first-line treatment for OC [3]. Most patients were subjected to relapse after surgery or develop resistance to chemotherapy drugs [4]. PTX contributes greatly to the OC treatment and often determines the prognosis of patients. The aim of this study is to investigate the mechanism of PTX resistance in OC
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