MiR-34a-5p/PD-L1 axis regulates cisplatin chemoresistance of ovarian cancer cells

Zuo, Ying; Zheng, Wenwen; Liu, J; Tang, Qiyun; Wang, S S; Yang, Xinggang

doi:10.4149/neo_2019_190202n106

Cited by 55 publications

(30 citation statements)

References 35 publications

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“…For example, miR-15a-3p suppresses the proliferation and invasion of ovarian cancer cells by targeting Twist1 (8). This suggests the possible application of miRNAs in cancer diagnosis, treatment or prognosis (9,10). Increasing evidence has indicated that miR-134 acts as a tumor suppressor by blocking the proliferation of various cancer cells through different signaling pathways (11,12).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-134-3p inhibits ovarian cancer progression by targeting flap structure-specific endonuclease 1 in vitro

Zhao

et al. 2020

Oncol Rep

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Ovarian cancer (OC) is one of the most lethal gynecological malignancies in the world. The aim of the present study was to examine the role of microRNA (miR)-134-3p in OC. Reverse transcription-quantitative PCR was used to measure the expression levels of miR-134-3p. Cell Counting Kit-8, TUNEL, flow cytometric and colony formation assays were performed to examine the effects of miR-134-3p on OC cell proliferation. Moreover, wound healing and Transwell assays were performed to examine the effects on migration and invasion. In addition, western blot analyses were used to assess protein expression. Finally, the target genes of miR-134-3p were analyzed by bioinformatics analysis and Dual-Luciferase reporter assay. The results revealed that miR-134-3p expression was low in OC cells compared with in normal ovarian cells. The overexpression of miR-134-3p decreased cell viability, facilitated cell apoptosis, inhibited cell proliferation and arrested the cell cycle in SKOV-3 and OVCAR-3 cells. Furthermore, transfection using a miR-134-3p mimic inhibited the migration and invasion of SKOV-3 and OVCAR-3 cells, and decreased the protein expression levels of cyclooxygenase-2, matrix metalloproteinase (MMP)2 and MMP9. Bioinformatics analysis indicated that one of the potential target genes of miR-134-3p was flap structure-specific endonuclease 1 (FEN1), which was confirmed by dual-luciferase reporter assay. Moreover, overexpression of miR-134-3p decreased the expression levels of FEN1 in SKOV-3 and OVCAR-3 cells. Additionally, overexpression of FEN1 reversed the effects of the miR-134-3p mimic on the proliferation, migration and invasion of SKOV-3 and OVCAR-3 cells. Overall, the findings of the present study demonstrated that miR-134-3p may inhibit OC cell proliferation, migration and invasion by directly targeting FEN1.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-134-3p inhibits ovarian cancer progression by targeting flap structure-specific endonuclease 1 in vitro

Zhao

et al. 2020

Oncol Rep

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“…Interestingly, our data showed that downregulation of miR-138-5p only partially reversed the HOTAIR silencing-mediated pro-apoptosis activity, suggesting that other miR-NAs or molecules may also contribute to the action of HOTAIR on chemosensitivity of ovarian cancer cells to DDP. Many miRNAs (such as miR-34a and miR-454) reported to be involved in regulating the chemosensitivity of ovarian cancer were regulated by HOTAIR [38][39][40][41], indicating that HOTAIR may also mediate chemoresistance of ovarian cancer cells by other miR-NAs and their target genes. Moreover, the efficacy of HOTAIR/miR-138-5p axis on the treatment in clinical studies needs further explorations.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of long non-coding RNA HOTAIR reverses cisplatin resistance of ovarian cancer cells through inhibiting miR-138-5p-regulated EZH2 and SIRT1

Zhang

Xue

et al. 2020

Biol Res

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Background: Cisplatin resistance (DDP-resistance) remains one of the major causes of poor prognosis in females with ovarian cancer. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of cellular processes, including chemoresistance. The aim of this study was to explore the role of HOX transcript antisense RNA (HOTAIR) in DDP-resistant ovarian cancer cells. Methods: DDP-resistant ovarian cancer cell lines (SKOV3/DDP and A2780/DDP) were established. Real-time PCR, western blot, dual-luciferase reporter assay, and flow cytometry were then used to evaluate the effect of HOTAIR/miR-138-5p axis on chemoresistance of DDP-resistant ovarian cancer cells to DDP. Results: We found that HOTAIR was upregulated in DDP-resistant cells, while miR-138-5p was downregulated. Knockdown of HOTAIR increased the expression of miR-138-5p in DDP-resistant cells and miR-138-5p is directly bound to HOTAIR. Upregulation of miR-138-5p induced by HOTAIR siRNA or by its mimics enhanced the chemosensitivity of DDP-resistant cells and decreased the expression of EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) and SIRT1 (sirtuin 1). Furthermore, the HOTAIR silencing-induced chemosensitivity of DDP-resistant cells was weakened by miR-138-5p inhibitor. Conclusions: These data demonstrate that HOTAIR acts as a sponge of miR-138-5p to prevent its binding to EZH2 and SIRT1, thereby promoting DDP-resistance of ovarian cancer cells. Our work will shed light on the development of therapeutic strategies for ovarian cancer treatment.

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“…Ebrahimiyan 37 , et al’s study showed that altered expression of survivin, regulated by miRNAs, such as miR-34a-5p, may result in apoptosis resistance and auto-reactivity in lymphocytes from patients and have important roles in systemic sclerosis pathogenicity. Zuo 38 et al’s study demostrated that miR-34a-5p negatively regulated the expression of PD-L1 by targeting its 3′-untranslated region and miR-34a-5p/PD-L1 axis regulated cis-diamminedichloroplatinum (DDP) chemoresistance of ovarian cancer cells. Also, Luo 39 et al’s study discovered that TP73‑AS1 contributed to proliferation, migration and DDP resistance but inhibited apoptosis of non-small cell lung cancer cells by upregulating TRIM29 and sponging miR‑34a‑5p.…”

Section: Discussionmentioning

confidence: 99%

Potential miRNA biomarkers for the diagnosis and prognosis of esophageal cancer detected by a novel absolute quantitative RT-qPCR method

Lin¹,

Chen²,

Lin³

et al. 2020

Sci Rep

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AbstractmiRNAs are expected to become potential biomarkers in the diagnosis and prognosis of Esophageal cancer (EC). Through a series of screening, miR-34a-5p, miR-148a-3p and miR-181a-5p were selected as EC-associated miRNAs. Based on AllGlo probe, a novel absolute quantitative RT-qPCR method with high sensitivity, specificity and accuracy was established for detecting miRNAs. Then the clinical significance of these 3 miRNAs was explored with 213 patients (166 cases with EC and 47 cases with benign diseases) and 170 normal controls. Compared with normal controls, the level of miR-34a-5p increased while miR-148a-3p and miR-181a-5p decreased in EC and benign patients (P < 0.001), and the level of miR-181a-5p in early EC patients was significantly lower (P < 0.001). According to logistic regression analysis, combined detection of miR-34a-5p, miR-148a-3p and Cyfra21-1 provided the highest diagnosis efficiency of 85.07% with sensitivity and specificity reaching 85.45% and 84.71%. Compared with preoperative samples, the level of miR-34a-5p decreased while miR-148a-3p and miR-181a-5p increased in postoperative samples (P < 0.001). Collectively, this first developed, novel absolute quantitative RT-qPCR method exhibits high application value in detecting miRNAs, miR-34a-5p, miR-148a-3p and miR-181a-5p may serve as potential biomarkers in the diagnosis and prognosis of EC, and miR-181a-5p probably could serve as a new biomarker for early EC.

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MiR-34a-5p/PD-L1 axis regulates cisplatin chemoresistance of ovarian cancer cells

Cited by 55 publications

References 35 publications

MicroRNA-134-3p inhibits ovarian cancer progression by targeting flap structure-specific endonuclease 1 in vitro

MicroRNA-134-3p inhibits ovarian cancer progression by targeting flap structure-specific endonuclease 1 in vitro

Knockdown of long non-coding RNA HOTAIR reverses cisplatin resistance of ovarian cancer cells through inhibiting miR-138-5p-regulated EZH2 and SIRT1

Potential miRNA biomarkers for the diagnosis and prognosis of esophageal cancer detected by a novel absolute quantitative RT-qPCR method

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