Liposomal Delivery of MicroRNA-7–Expressing Plasmid Overcomes Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-Resistance in Lung Cancer Cells

Rai, Kammei; Takigawa, Nagio; Ito, Sachio; Kashihara, Hiromi; Ichihara, Eiki; Yasuda, Tatsuji; Shimizu, Kenji; Tanimoto, Mitsune; Kiura, Katsuyuki

doi:10.1158/1535-7163.mct-11-0220

Cited by 116 publications

(79 citation statements)

References 43 publications

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“…miR-7 expression was found to be repressed in lung cancer tissues (7,14). Moreover, miR-7 was able to suppress the growth and metastatic potential of human lung cancer cells in vitro (15). Our previous studies also demonstrated that overexpression of miR-7 reduced the growth and metastasis of human lung cancer cells in vivo (16,17).…”

Section: Introductionmentioning

confidence: 79%

Promoter mutation of tumor suppressor microRNA-7 is associated with poor prognosis of lung cancer

Zhao

Wang

Liao

et al. 2015

Molecular and Clinical Oncology

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Abstract. The significance of promoter mutations of microRNAs (miRNAs) in lung cancer is poorly understood. Recent evidence demonstrated that miRNA-7 (miR-7), a unique member of the miRNA family, exhibited decreased expression and has emerged as an important regulator in lung tumorigenesis. However, the mechanism underlying the downregulation of miR-7 in lung cancer remains largely unknown. In this study, we investigated the sites of mutation of the miR-7 promoter in lung cancer tissues using DNA sequencing. We identified a G→C change at the -617 site (25/39, 64.1%) and an A→G change at the -604 site (20/39, 51.3%) in the miR-7 promoter region in lung cancer tissues. Moreover, the expression of miR-7 in cancer tissue with promoter site mutations was lower compared with that in cancer tissue without mutations (P<0.05). Furthermore, we demonstrated that mutations at these sites may decrease the activity of the miR-7 promoter and alter the expression of miR-7. Notably, mutations at these sites of the miR-7 promoter were found to be closely associated with poor prognosis of lung cancer patients (P=0.037). These data may provide novel insight on the altered expression of specific miRNA molecules in lung cancer and ultimately prove to be helpful in the development of prognostic and therapeutic strategies against lung cancer.

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Section: Introductionmentioning

confidence: 79%

Promoter mutation of tumor suppressor microRNA-7 is associated with poor prognosis of lung cancer

Zhao

Wang

Liao

et al. 2015

Molecular and Clinical Oncology

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“…The main mechanisms of acquired resistance to these drugs include secondary mutations in EGFR, such as the gatekeeper T790M mutation, detected in approximatively 50% of resistant cases; and amplification of the MET oncogene [98], observed in 5-20% of resistant cases [99]. This resistance can be overcome by EGFR inhibition by miR-7, which targets three sites in the 3'-untranslated region of EGFR mRNA [100]. Recent evidence showed that several miRNAs can be involved in resistance to different drugs targeting EGFR ( Table 2).…”

Section: Mirnas and Resistance To Targeted Therapy In Nsclcmentioning

confidence: 99%

Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer

Rolfo¹,

Fanale²,

Hong³

et al. 2014

CPB

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Despite recent advances in understanding the cancer signaling pathways and in developing new therapeutic strategies, non-small cell lung cancer (NSCLC) shows grim prognosis and high incidence of recurrence. Insufficient disruption of oncogenic signaling and drug resistance are the most common causes of tumor recurrence. Drug resistance, intrinsic or acquired, represents a main obstacle in NSCLC therapeutics by limiting the efficacy both of conventional chemotherapeutic compounds and new targeted agents. Therefore, novel and more innovative approaches are required for treatment of this tumor. MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression by sequence-specific targeting of mRNAs causing mRNA degradation or translational repression. Accumulating evidence suggests that impairment of candidate miRNAs may be involved in the acquisition of tumor cell resistance to conventional chemotherapy and novel biological agents by affecting the drug sensitivity of cancer cells. The modulation of these miRNAs, using antagomiRs or miRNA mimics, can restore key gene networks and signaling pathways, and optimize anticancer therapies by inhibition of tumor cell proliferation and increasing the drug sensitivity. Therefore, miRNA-based therapeutics provides an attractive anti-tumor approach for developing new and more effective individualized therapeutic strategies, improving drug efficiency, and for predicting the response to different anticancer drugs. In this review, we present an overview on the role of miRNAs in resistance mechanisms of NSCLC, discussing the main studies on the aberrations in apoptosis, cell cycle and DNA damage repair pathways, as well as in novel drug targets.

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“…58 Interestingly, liposomal delivery of miRNA-7-expressing plasmid overcame EGFR-TKI resistance in lung cancer cells. 59 Solid LNPs loaded with anti-miRNA oligonucleotides (AMOs) increased the inhibitory effect of miRNA-21 on the proliferation, migration, and invasion of human lung cancer cells. 60 However, the further in vivo data were not reported in the above two studies.…”

Section: Systemic Ncrna Delivery Strategies In Lung Cancer Treatmentmentioning

confidence: 99%

Long and short noncoding RNAs in lung cancer precision medicine: Opportunities and challenges

et al. 2017

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The long and short noncoding RNAs have been involved in the molecular diagnosis, targeted therapy, and predicting prognosis of lung cancer. Utilizing noncoding RNAs as biomarkers and systemic RNA interference as an innovative therapeutic strategy has an immense likelihood to generate novel concepts in precision oncology. Targeting of RNA interference payloads such as small interfering RNAs, microRNA mimetic, or anti-microRNA (antagomirs) into specific cell types has achieved initial success. The clinical trials of noncoding RNA-based therapies are on the way with some positive results. Many attempts are done for developing novel noncoding RNA delivery strategies that could overcome systemic or local barriers. Furthermore, it precipitates concerted efforts to define the molecular subtypes of lung cancer, characterize the genomic landscape of lung cancer subtypes, identify novel therapeutic targets, and reveal mechanisms of sensitivity and resistance to targeted therapies. These efforts contribute a visible effect now in lung cancer precision medicine: patients receive molecular testing to determine whether their tumor harbors an actionable come resistance to the first-generation drugs are in clinical trials, and drugs targeting the immune system are showing activity in patients. This extraordinary promise is tempered by the sobering fact that even the newest treatments for metastatic disease are rarely curative and are effective only in a small fraction of all patients. Thus, ongoing and future efforts to find new vulnerabilities of lung cancers unravel the complexity of drug resistance, increase the efficacy of immunotherapies, and perform biomarker-driven clinical trials are necessary to improve the outcome of lung cancer patients.

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Liposomal Delivery of MicroRNA-7–Expressing Plasmid Overcomes Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-Resistance in Lung Cancer Cells

Cited by 116 publications

References 43 publications

Promoter mutation of tumor suppressor microRNA-7 is associated with poor prognosis of lung cancer

Promoter mutation of tumor suppressor microRNA-7 is associated with poor prognosis of lung cancer

Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer

Long and short noncoding RNAs in lung cancer precision medicine: Opportunities and challenges

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