<p>LncRNA MALAT1 Regulates the Progression and Cisplatin Resistance of Ovarian Cancer Cells via Modulating miR-1271-5p/E2F5 Axis</p>

Abstract

Background: Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were reported to be related to the development of ovarian cancer (OC). In this study, the functional mechanisms of lncRNA metastasis associated with lung adenocarcinoma transcript 1 (MALAT1) and microRNA-1271-5p (miR-1271-5p) were explored in OC. Methods: The level of MALAT1, miR-1271-5p, or E2F transcription factor 5 (E2F5) was detected by qRT-PCR. MTT assay, flow cytometry analysis and transwell migration and invasion assays were performed to determine cell proliferation, apoptosis, migration and invasion, respectively. E2F5 protein expression was detected by Western blot. The interaction between miR-1271-5p and MALAT1 or E2F transcription factor 5 (E2F5) was confirmed by the dual-luciferase reporter assay. Results: MALAT1 and E2F5 level were increased, while miR-1271-5p level was decreased in cisplatin (DDP)-resistant OC tissues and cells. MALAT1 knockdown or miR-1271-5p upregulation decreased IC 50 of cisplatin, and inhibited cell proliferation, migration, invasion, and facilitated cell apoptosis in DDP-resistant OC cells. Moreover, MALAT1 sponged miR-1271-5p to upregulate E2F5 expression. Besides, MALAT1 knockdown decreased DDP resistance, inhibited cell proliferation, migration, invasion, and promoted cell apoptosis by sponging miR-1271-5p to downregulate E2F5 expression in DDP-resistant OC cell. Conclusion: We demonstrated that MALAT1 mediated DDP-resistant OC development through miR-1271-5p/E2F5 axis, providing the theoretical basis for OC therapy.

lncRNA MALAT1 participates in metformin inhibiting the proliferation of breast cancer cell

“…In cisplatinresistant ovarian cancer tissues and cells, MALAT1 was reported to be increased and knock-down of which could decrease cisplatin resistance. 17 In renal cell carcinoma, sunitinib resistance is showed to be positive associated with dramatical up-regulation of MALAT1, and the chemoresistance could be reversed by MALAT1 knock-down. 18 Therefore, regulating the expression of MALAT1 would be a valuable means to repurposing metformin in breast cancer treatment.…”

“…In addition, high expression of MALAT1 is always related to chemosensitivity. In cisplatin‐resistant ovarian cancer tissues and cells, MALAT1 was reported to be increased and knock‐down of which could decrease cisplatin resistance 17 . In renal cell carcinoma, sunitinib resistance is showed to be positive associated with dramatical up‐regulation of MALAT1, and the chemoresistance could be reversed by MALAT1 knock‐down 18 .…”

HOTTIP-miR-205-ZEB2 Axis Confers Cisplatin Resistance to Ovarian Cancer Cells

“…Seeking a possible role of lncRNAs in cisplatin resistance, a number of lncRNAs have already been evaluated for their possible involvement in cisplatin sensitivity/resistance. Examples are UCA1 ( Wang F. et al, 2015 ; Li Z. et al, 2019 ), HOTAIR ( Wang Y. et al, 2015 ; Li et al, 2016 ; Yu et al, 2018 ; Zhang et al, 2020 ), PVT1 ( Liu et al, 2015 ; Chen et al, 2021 ), H19 ( Zheng et al, 2016 ; Sajadpoor et al, 2018 ; Wu et al, 2019 ), ENST00000457645 ( Yan et al, 2017 ), MEG3 ( Zhang J. et al, 2017 ), ANRIL ( Zhang D. et al, 2017 ; Miao et al, 2019 ), RP11-135L22.1 ( Zou et al, 2018 ), MALAT1 ( Bai et al, 2018 ; Wang Y. et al, 2020 ; Taheri et al, 2021 ), Linc00312 ( Zhang et al, 2018 ), EBIC ( Xu et al, 2018 ), HOXD-AS1 ( Chi et al, 2018 ), PANDAR ( Wang et al, 2018 ), CASC11 ( Shen et al, 2019 ), LINC00152 ( Zou and Li, 2019 ), NCK1-AS1 ( Chang et al, 2020 ), LINC01125 ( Guo and Pan, 2019 ), CCAT1 ( Wang D.Y. et al, 2020 ), NEAT1 ( Zhu et al, 2020 ), CHRF ( Tan et al, 2020 ), ZEB1-AS1 ( Dai et al, 2021 ), TRPM2-AS ( Ding et al, 2021 ), and LOC102724169 ( Zhou et al, 2021 ).…”

“…The lncRNAs-based epigenetic signature can also possibly help stratify ovarian cancer patients with implications in precision medicine ( Liu et al, 2017 ). A number of lncRNAs, such as HOTAIR ( Wang Y. et al, 2015 ; Li et al, 2016 ; Yu et al, 2018 ; Zhang et al, 2020 ) and MALAT1 ( Bai et al, 2018 ; Wang Y. et al, 2020 ; Taheri et al, 2021 ) have been investigated for their possible role in regulating sensitivity to cisplatin of ovarian cancers. In this study, we hypothesized a possible role of lncRNA HOTTIP (HOXA transcript at the distal tip) in the cisplatin resistance of ovarian cancer cells.…”

(In)Distinctive Role of Long Non-Coding RNAs in Common and Rare Ovarian Cancers

“…Other signaling pathways which are directly or indirectly affected by MALAT1 include the PI3K-AKT pathway [186] and the ERK/MAPK pathway [187]. MALAT1 has also been implicated in drug resistance of OC, as it was found upregulated in cisplatin-resistant OC cells, where it sponges miR-1271-5p, leading to upregulation of E2F5 and increased proliferation, migration, and invasion [188]. MALAT1 is also upregulated in OC spheroids when compared to their adherent counterparts, suggesting a role of MALAT1 in cancer cell stemness [189].…”