Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin

Feng, Yeqian; Zou, Wen; Hu, Chunhong; Li, Guiyuan; Zhou, Shenghua; He, Yan; Ma, Fengwang; Deng, Chao; Sun, Lili

doi:10.1016/j.abb.2017.05.001

Cited by 107 publications

(90 citation statements)

References 39 publications

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“…Expression of miR-21 is up-regulated in various human tumor tissues and cells, such as brain glioma, ovarian cancer, bladder cancer, prostate cancer, lung cancer, breast cancer, thyroid cancer, esophageal cancer, liver cancer, bile duct cancer, pancreatic cancer, colorectal cancer, gastric cancer, and B cell lymphoma. miR-21 participates in the proliferation, migration, invasion, differentiation and apoptosis of tumor cells (26,27). In addition, miR-21 is involved in the regulation of multiple downstream target genes such as PTEN, PDCD4, RECK, and TIMP-3 (21,28).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑21 promotes the proliferation, migration and invasion of non‑small cell lung cancer A549 cells by regulating autophagy activity via AMPK/ULK1 signaling pathway

Zeng

et al. 2018

Exp Ther Med

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Abstract. The present study investigated the expression of microRNA (miR)-21 in non-small cell lung cancer (NSCLC) tissues, its biological functions and mechanism of autophagy regulation. A total of 46 patients with NSCLC were enrolled in the present study. To measure the expression of miR-21, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed. NSCLC A549 cells were transfected with miR-negative control (NC), miR-21 mimics or inhibitor. The CCK-8 assay was used to investigate the proliferation of A549 cells. To study migration and invasion abilities of A549 cells, The Transwell assay was performed. In addition, to determine the expression levels of ULK1, LC3B, AMPKα, p-AMPKα and p62 proteins, western blotting was conducted and laser confocal microscopy was performed to observe the formation of autophagosomes in A549 cells. To explore whether miR-21 regulates the biological functions of A549 cells via autophagy, an autophagy inhibitor, 3-MA, or agonist, rapamycin, were used in a rescue assay. Results indicated that miR-21 expression in NSCLC tissues was enhanced, and closely correlated with the occurrence and development of NSCLC. In vitro experiments showed that miR-21 mimics promoted the proliferation, migration and invasion of A549 cells, while miR-21 inhibitor inhibited these biological functions. Western blotting indicated that miR-21 upregulated autophagy marker LC3BⅡ protein, but downregulated p62 protein. Laser confocal microscopy showed that miR-21 activated autophagy of A549. Rescue experiments indicated that autophagy reversed the effect of miR-21 on the proliferation, migration and invasion of A549 cells. Western blotting data suggested that autophagy-related AMPK/ULK1 signaling pathway was activated by miR-21, and interference or overexpression of ULK1 reversed the biological functions of miR-21. The present study demonstrated that miR-21 expression in NSCLC tissues was upregulated and positively correlated with lymphatic metastasis and clinical staging. In addition, miR-21 regulated autophagy activity of NSCLC A549 cells via AMPK/ULK1 signaling pathway, and promoted the proliferation, migration and invasion of NSCLC A549 cells.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑21 promotes the proliferation, migration and invasion of non‑small cell lung cancer A549 cells by regulating autophagy activity via AMPK/ULK1 signaling pathway

Zeng

et al. 2018

Exp Ther Med

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“…After 15 of these had been thoroughly evaluated, 7 were excluded because they did not meet the inclusion criteria. Finally, 8 articles [21-28] were included in our meta-analysis. The detailed process of study, search, and selection is presented in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…These cancers ranged from an early stage to advanced clinical stages (I, II, III, and IV). Of the 8 studies, 3 included a follow-up of greater than or equal to 60 months [23, 27, 28]; the remaining 5 studies covered less than 5 years [21, 22, 24-26]. The expression of lncRNA CASC2 in all eligible studies was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and normalized relative to GAPDH or RNU6B using the 2 –ΔΔCt method.…”

Section: Resultsmentioning

confidence: 99%

“…Now increasing numbers of studies have shown that CASC2 is also significantly downregulated in other cancers, such as hepatocellular carcinoma, colorectal cancer, and bladder cancer [17-19], and it could act as a tumor suppressor with implications for diagnosis and therapy [20]. Numerous researchers have reported that CASC2 is implicated in tumor initiation and progression and has shown a potential for predicting cancer prognosis [21-23]. However, up to now there has been no specific meta-analysis to systematically elucidate the prognostic value of CASC2 in cancers.…”

Section: Introductionmentioning

confidence: 99%

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Low Expression of LncRNA Cancer Susceptibility Candidate 2 and its Clinical Significance in Cancer Tissues

Zhu

Liu

Chen

2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is downregulated in various cancers and involved in both tumorigenesis and progression. The aim of this study was to assess the prognostic value of lncRNA CASC2 in cancer patients. Methods: We searched the Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and the Wanfang database to identify studies evaluating the prognostic value of lncRNA CASC2 in cancer patients. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects/random-effects models. Results: A total of eight studies were included. The combined results showed that lncRNA CASC2 was significantly associated with decreased overall survival (OS) (HR = 0.37, 95% CI, 0.27–0.46, P < 0.001). Subgroup analyses further indicated that low expression of lncRNA CASC2 predicted decreased OS in cancer patients. Additionally, low CASC2 expression levels in cancer tissues appeared to be correlated with advanced clinical staging (OR = 3.32, 95% CI, 2.29–4.80, P < 0.001). Conclusions: Low CASC2 expression appears to be predictive of poor OS and advanced tumor stage in multiple cancers. CASC2 expression may serve as unfavorable prognostic factor for clinical outcomes in cancer patients.

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“…Zheng et al (2016) demonstrated that ceRNA networks of CYP4Z1 and pseudogene CYP4Z2P confer tamoxifen resistance in breast cancer. Feng et al (2017) indicated that CASC2 up-regulates PTEN as a ceRNA of miR-21 and plays an important role in cervical cancer sensitivity to cisplatin. Therefore, understanding this novel RNA cross talk will lead to significant insight into gene interactions and has implication in drug responses.…”

Section: Introductionmentioning

confidence: 99%

Inferences of individual drug responses across diverse cancer types using a novel competing endogenous RNA network

Zhang

Zhou

et al. 2018

Molecular Oncology

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Differences in individual drug responses are an obstacle to progression in cancer treatment, and predicting responses would help to plan treatment. The accumulation of cancer molecular profiling and drug response data provides opportunities and challenges to identify novel molecular signatures and mechanisms of tumor responsiveness to drugs. This study evaluated drug responses with a competing endogenous RNA (ceRNA) system that depended on competition between diverse RNA species. We identified drug response‐related ceRNA (DRCEs) by combining the sequence and expression data of long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA), and the survival data of cancer patients treated with drugs. We constructed a patient–drug two‐layer integrated network and used a linear weighting method to predict individual drug responses. DRCEs were found to be significantly enriched in known cancer and drug‐associated data resources, involved in biological processes known to mediate drug responses, and correlated to drug activity in cancer cell lines. The dysregulation of DRCE expression influenced drug response‐associated functions and pathways, suggesting DRCEs as potential therapeutic targets affecting drug responses. A further case study in breast invasive carcinoma (BRCA) found that DRCE expression was consistent with the drug response pattern and the aberrant expression of the two NEAT1‐related DRCEs may lead to poor response to tamoxifen therapy for patients with TP53 mutations. In summary, this study provides a framework for ceRNA‐based evaluation of clinical drug responses across multiple cancer types. Understanding the underlying molecular mechanisms of drug responses will allow improved response to chemotherapy and outcomes of cancer treatment.

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Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin

Cited by 107 publications

References 39 publications

MicroRNA‑21 promotes the proliferation, migration and invasion of non‑small cell lung cancer A549 cells by regulating autophagy activity via AMPK/ULK1 signaling pathway

MicroRNA‑21 promotes the proliferation, migration and invasion of non‑small cell lung cancer A549 cells by regulating autophagy activity via AMPK/ULK1 signaling pathway

Low Expression of LncRNA Cancer Susceptibility Candidate 2 and its Clinical Significance in Cancer Tissues

Inferences of individual drug responses across diverse cancer types using a novel competing endogenous RNA network

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