Long non-coding RNA NEAT1 contributes to docetaxel resistance of prostate cancer through inducing RET expression by sponging miR-34a

Tian, Xin; Zhang, Guangwei; Zhao, Hui; Li, Yang; C, Zhu

doi:10.1039/c7ra06107b

Cited by 12 publications

(7 citation statements)

References 45 publications

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“…In cisplatin-resistant gastric cancer cells, NEAT1 expression was significantly upregulated accompanied with the induction of P-glycoprotein, which is a multidrug resistance-associated protein 42 . NEAT1 is also reported to contribute to docetaxel resistance through inducing RET expression by sponging miR-34a in prostate cancer 43 . In nasopharyngeal carcinoma, NEAT1 enhanced the cisplatin resistance by targeting Rsf-1 and Ras-mitogen-associated protein kinase signaling pathway 44 .…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness

et al. 2019

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Triple-negative breast cancer (TNBC) is a malignant subtype of breast cancer with the absence of targeted therapy, resulting in poor prognosis in patients. Chemotherapy remains the mainstay of treatment for TNBC; however, development of drug resistance is the main obstacle for successful treatments. In recent years, long non-coding RNA (lncRNA) has been implicated in multiple biological functions in various diseases, particularly cancers. Accumulating evidence suggested that lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) expression is dysregulated in many human cancers and thus is a useful prognostic marker for cancer patients. Nevertheless, the mechanism of how NEAT1 confers drug resistance in TNBC is still largely unknown. We performed lncRNA profiling by the LncRNA Profiler qPCR Array Kit in normal control (NC) and breast cancers (BC) blood samples and further validated in a larger cohort of samples by qRT-PCR. Gene expression level and localization were investigated by qRT-PCR, western blotting, and immunofluorescence staining. Flow cytometric analysis was carried out to detect cancer stem cells. Functional studies were performed both in vitro and in vivo xenograft model. Among 90 lncRNAs, NEAT1 was highly expressed in the blood samples of breast cancer patients than in NC. In particular, the expression of NEAT1 was higher in TNBC tissues than other subgroups. Functional studies revealed that NEAT1 conferred oncogenic role by regulating apoptosis and cell cycle progression in TNBC cells. We identified that knockdown of NEAT1 sensitized cells to chemotherapy, indicating the involvement in chemoresistance. Importantly, shNEAT1 reduced stem cell populations such as CD44+/CD24−, ALDH+, and SOX2+, implicating that NEAT1 was closely related to cancer stemness in TNBC. Our data highlighted the roles of NEAT1 chemoresistance and cancer stemness, suggesting that it could be used as a new clinical therapeutic target for treating TNBC patients especially those with drug resistance.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness

et al. 2019

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“…As reported by Wen et al,22 miR-34a enhanced paclitaxel chemotherapy in paclitaxel-resistant PC cells. Moreover, miR-34a attenuated DTX resistance in prostate cancer through repressing RET 23…”

Section: Discussionmentioning

confidence: 99%

<p>Long noncoding RNA DANCR contributes to docetaxel resistance in prostate cancer through targeting the miR-34a-5p/JAG1 pathway</p>

Ma¹,

Fan²,

Ren³

et al. 2019

OTT

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Background: Chemotherapy is one of the available options for prostate cancer (PC). However, the acquisition of chemoresistance has become a major cause of chemotherapy failure. The long noncoding RNA DANCR is demonstrated to serve as an oncogene in various human cancers, including PC. However, the potential role of DANCR in docetaxel (DTX) resistance of PC and its underlying mechanism remains unclear. Methods: The abundance of DANCR, miR-34a-5p, and JAG1 mRNA was examined by quantitative reverse transcription PCR. The Cell Counting Kit-8 (CCK8) was used to determine the 50% inhibitory concentration value. Cell viability was evaluated by CCK8 and colony-formation assays. Transwells were utilized to analyze cell migration and invasion ability. The protein levels of LRP, P-gp, MRP1, and JAG1 were measured by Western blot assay. The target relationship between DANCR and miR-34a-5p, as well as miR-34a-5p and JAG1, was demonstrated by dual-luciferase, RNA immunoprecipitation, and RNA pull-down analysis. Tumor xenograft was undertaken to confirm the effect of DANCR on DTX resistance in PC. Results: DANCR and JAG1 were significantly upregulated, but miR-34a-5p was downregulated in DTX-resistant PC. Silencing of DANCR improved the DTX efficacy in DTX-resistant PC cells. DANCR served as a competing endogenous RNA of miR-34a-5p, leading to the derepression of miR-34a-5p target JAG1, which eventually triggered the resistance to DTX in DTX-tolerated PC. Conclusion: The DANCR/miR-34a-5p axis enhanced DTX resistance of PC via targeting JAG1, providing a novel insight to improve chemotherapy for PC.

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“…NEAT1 knockdown re-sensitizes the resistant PC cells to docetaxel, which may be associated with the sponging of miR-34a-5p. 109,131 Tyrosine kinase inhibitors A variety of protein kinases, including receptor tyrosine kinases such as VEGF receptors (VEGFRs) engage in tumor progression. A series of tyrosine kinase inhibitors (TKIs) have been developed for the systematic treatment of various types of cancers.…”

Section: Cytotoxic Drugsmentioning

confidence: 99%

The functional role of long noncoding RNA in resistance to anticancer treatment

Tan

Chan

et al. 2020

Ther Adv Med Oncol

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Chemotherapy is one of the fundamental methods of cancer treatment. However, drug resistance remains the main cause of clinical treatment failure. We comprehensively review the newly identified roles of long noncoding RNAs (lncRNAs) in oncobiology that are associated with drug resistance. The expression of lncRNAs is tissue-specific and often dysregulated in human cancers. Accumulating evidence suggests that lncRNAs are involved in chemoresistance of cancer cells. The main lncRNA-driven mechanisms of chemoresistance include regulation of drug efflux, DNA damage repair, cell cycle, apoptosis, epithelial-mesenchymal transition (EMT), induction of signaling pathways, and angiogenesis. LncRNA-driven mechanisms of resistance to various antineoplastic agents have been studied extensively. There are unique mechanisms of resistance against different types of drugs, and each mechanism may have more than one contributing factor. We summarize the emerging strategies that can be used to overcome the technical challenges in studying and addressing lncRNA-mediated drug resistance.

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Long non-coding RNA NEAT1 contributes to docetaxel resistance of prostate cancer through inducing RET expression by sponging miR-34a

Abstract: Nuclear paraspeckle assembly transcript 1 (NEAT1) was demonstrated to serve as a carcinogenic long non-coding RNA (lncRNA) in multiple tumors including prostate cancer (PC).

Cited by 12 publications

References 45 publications

Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness

Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness

<p>Long noncoding RNA DANCR contributes to docetaxel resistance in prostate cancer through targeting the miR-34a-5p/JAG1 pathway</p>

The functional role of long noncoding RNA in resistance to anticancer treatment

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