The role and mechanisms of action of microRNAs in cancer drug resistance

Si, Wengong; Shen, Jingnan; Zheng, Huilin; Fan, Weimin

doi:10.1186/s13148-018-0587-8

Cited by 548 publications

(414 citation statements)

References 247 publications

(249 reference statements)

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“…Our initial study presented here ignores noncoding genomic alterations. However, noncoding RNAs such as EGRF-AS1 and activating cis elements such as enhancers have previously been implicated in evasion of drug response (67)(68)(69). The intergenic mutations with high allele frequency are present in our provided datasets and provide opportunity for reanalysis or for querying by those interested in a specific noncoding RNA or enhancer.…”

Section: Resultsmentioning

confidence: 99%

In vitroevolution and whole genome analysis to study chemotherapy drug resistance in haploid human cells

Carolino

et al. 2020

Preprint

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Understanding general mechanisms of chemotherapy resistance can assist with the design of new drugs and guide cancer treatment decisions. Here we applied in vitro evolution and whole genome analysis (IVIEWGA) to the human, near-haploid cell line (HAP-1) to directly identify resistance alleles. Clones (28) resistant to five different anticancer drugs (doxorubicin, gemcitabine, etoposide, topotecan, and paclitaxel), were evolved and compared to their isogenic parents via whole genome and whole exome sequencing (WES). High frequency alleles predicted to change protein sequence, or alleles which appeared in the same gene for multiple independent selections with the same compound were identified in only 21 genes: The set included clinically-relevant resistance genes or drug targets (TOP1, TOP2A, DCK, WDR33, SLCO3A1), as well as new genes (SLC13A4). In addition, some lines carried structural variants that encompassed additional known resistance genes (ABCB1, WWOX and RRM1). Gene expression knockdown and knockout experiments (via shRNA and CRISPR-Cas9 respectively) of 10 validation targets showed a high degree of specificity and accuracy in our calls and demonstrates that the same drug resistance mechanisms found in diverse clinical samples can be evolved, identified and studied in an isogenic background in the laboratory.

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Section: Resultsmentioning

confidence: 99%

In vitroevolution and whole genome analysis to study chemotherapy drug resistance in haploid human cells

Carolino

et al. 2020

Preprint

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“…Drug resistance to chemotherapeutic drugs or targeted medicines is an obstacle encountered in NSCLC treatment [21,22]. Besides mRNAs, lncRNAs and miRNAs have been reported to play an important part in the drug resistance of cancers [23,24,25]. In fact, some lncRNAs and miRNAs have been demonstrated to take part in drug resistance to chemotherapeutic drugs or targeted medicines of NSCLC, including lncRNA TUG1 related to 5-fluorouracil resistance [26], miR-15b related to sunitinib resistance [27].…”

Section: Discussionmentioning

confidence: 99%

Analysis of lncRNA, miRNA and mRNA-associated ceRNA networks and identification of potential drug targets for drug-resistant non-small cell lung cancer

Kong¹,

Hu²,

Yuan³

et al. 2020

J. Cancer

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Background: Drug resistance to chemotherapeutic drugs or targeted medicines is an obstacle encountered in the treatment of non-small-cell lung cancer (NSCLC). However, the mechanisms of competing endogenous RNA (ceRNA) on the drug resistance in NSCLC are rarely reported. In this paper, the comprehensive expression profiles of lncRNAs and mRNAs in drug-resistant NSCLC cells were obtained by RNA sequencing. Methods: The dysregulated lncRNAs, miRNAs and mRNAs in drug-resistant NSCLC cell lines were identified by RNA-sequencing and bioinformatics methods. Results: A total of 39 dysregulated lncRNAs and 650 dysregulated mRNAs were identified between drug-resistant NSCLC cell lines and their parental cell lines. Additionally, 33 lncRNA-miRNA-mRNA pathways in the ceRNA network in drug-resistant NSCLC were constructed through bioinformatics methods and ceRNA regulatory rules. These comprised 12 dysregulated lncRNAs, five dysregulated miRNAs, and eight dysregulated mRNAs. In addition, lncRNA ATP2B1/miR-222-5p/TAB2 and lncRNA HUWE1/miR-222-5p/TAB2 were identified as potential ceRNA networks involved in drug resistance to NSCLC. Conclusions: The current study provides a promising therapeutic strategy against the lncRNA-miRNA-mRNA ceRNA regulatory network for NSCLC treatment and deepens our comprehension of the ceRNA regulatory mechanisms related to drug resistance to NSCLC.

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“…Besides, mature miRNAs have been reported to impede the expression of targets by targeting them . MicroRNAs occupy a crucial position in various biological processes, including tumor metastasis . Recent studies have shown that many miRNAs, such as microRNA‐612 and miRNA‐621, function as tumor suppressors in NSCLC by regulating target genes .…”

Section: Introductionmentioning

confidence: 99%

“…16 MicroRNAs occupy a crucial position in various biological processes, including tumor metastasis. 17 Recent studies have shown that many miRNAs, such as microRNA-612 and miRNA-621, function as tumor suppressors in NSCLC by regulating target genes. 18,19 A previous study found that circFGFR3 facilitates NSCLC progression via targeting miR-22-3p.…”

Section: Introductionmentioning

confidence: 99%

LncRNA NNT‐AS1 promotes non‐small cell lung cancer progression through regulating miR‐22‐3p/YAP1 axis

Zhang

Xia

2020

Thoracic Cancer

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Background Lung cancer is the leading cause of cancer‐related mortality worldwide. Studies have demonstrated that long noncoding RNA nicotinamide nucleotide transhydrogenase‐antisense RNA1 (NNT‐AS1) functioned as an oncogene in most malignancies, including non‐small cell lung cancer (NSCLC). This study aimed to investigate the underlying mechanisms of NNT‐AS1 in NSCLC progression. Methods The levels of NNT‐AS1, miR‐22‐3p and Yes‐associated protein (YAP1) were detected by qRT‐PCR in NSCLC tissues and cells. Kaplan‐Meier analysis was conducted to analyze the correlation between NNT‐AS1 expression and overall survival of NSCLC patients. Cell proliferation was evaluated by MTT assay. Cell migration and invasion were assessed using transwell assay. The protein levels of YAP1 and EMT‐related proteins were detected by western blot. The molecular mechanism was predicted by starBase2.0 and validated by dual‐luciferase reporter assay or RNA pull‐down assay. Xenograft analysis was carried out to analyze tumor growth in vivo. Results We found that the levels of NNT‐AS1 and YAP1 were enhanced, while miR‐22‐3p expression was decreased in NSCLC tissues and cells. High NNT‐AS1 expression was correlated with poor prognosis. NNT‐AS1 knockdown impeded proliferation, migration, invasion and EMT of NSCLC cells. NNT‐AS1 targeted miR‐22‐3p, and YAP1 was a target of miR‐22‐3p in NSCLC cells. Furthermore, NNT‐AS1 facilitated the progression of NSCLC by regulating miR‐22‐3p/YAP1 axis. NNT‐AS1 knockdown repressed tumor growth in vivo. Conclusion NNT‐AS1 facilitated proliferation, migration, invasion and EMT of NSCLC cells by sponging miR‐22‐3p and regulating YAP1 expression, which might provide a potential biomarker and therapeutic target for NSCLC.

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The role and mechanisms of action of microRNAs in cancer drug resistance

Cited by 548 publications

References 247 publications

In vitroevolution and whole genome analysis to study chemotherapy drug resistance in haploid human cells

In vitroevolution and whole genome analysis to study chemotherapy drug resistance in haploid human cells

Analysis of lncRNA, miRNA and mRNA-associated ceRNA networks and identification of potential drug targets for drug-resistant non-small cell lung cancer

LncRNA NNT‐AS1 promotes non‐small cell lung cancer progression through regulating miR‐22‐3p/YAP1 axis

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