Knockdown of ANLN by lentivirus inhibits cell growth and migration in human breast cancer

Zhou, Wei‐Fang; Zhan, Wang; Shen, Ni; Pi, Weiwei; Jiang, Weixiong; Huang, Juan; Hu, Yuanyang; Li, Xiong; Sun, Lun‐Quan

doi:10.1007/s11010-014-2200-6

Cited by 83 publications

(78 citation statements)

References 26 publications

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“…Similar to the recently published findings by Zhou et al [14], we found that transient knockdown of ANLN protein expression in breast cancer cell lines resulted in a significant accumulation of cells in the G2/M phase of the cell cycle. Although experiments performed on only two different cell lines with differences in ER expression do not allow for general conclusions, we found that the impact of ANLN on these two breast cancer cells were similar, independent of ER status.…”

Section: Discussionsupporting

confidence: 92%

“…Using multivariable cox regression analysis, ANLN was suggested as an independent prognostic factor for BCSS following adjustment for tumor size, nodal status, tumor grade, hormone receptor status, HER2 status, Ki-67, tumor type, age and the proteins PDZ-Domain Containing 1 (PDZK1) and PDZ-Binding Kinase (PBK). In a recent study based on a cohort consisting of 71 patients diagnosed with primary breast cancer, the rate of ANLN expression was shown to be significantly higher in breast cancer compared to normal breast tissue [14]. In this study, ANLN knockdown was also shown to inhibit cell migration, colony formation and cell cycle progression.…”

Section: Introductionmentioning

confidence: 53%

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ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer

et al. 2016

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BackgroundAnillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer. The objective of the current study was to further explore the prognostic and functional value of ANLN as a single biomarker in breast cancer.MethodsImmunohistochemical assessment of ANLN protein expression was performed in two well characterized breast cancer cohorts (n = 484) with long-term clinical follow-up data and the results were further validated at the mRNA level in a publicly available transcriptomics dataset. The functional relevance of ANLN was investigated in two breast cancer cell lines using RNA interference.ResultsHigh nuclear fraction of ANLN in breast tumor cells was significantly associated with large tumor size, high histological grade, high proliferation rate, hormone receptor negative tumors and poor prognosis in both examined cohorts. Multivariable analysis showed that the association between ANLN and survival was significantly independent of age in cohort I and significantly independent of proliferation, as assessed by Ki-67 expression in tumor cells, age, tumor size, ER and PR status, HER2 status and nodal status in cohort II. Analysis of ANLN mRNA expression confirmed that high expression of ANLN was significantly correlated to poor overall survival in breast cancer patients. Consistent with the role of ANLN during cytokinesis, transient knock-down of ANLN protein expression in breast cancer cell lines resulted in an increase of senescent cells and an accumulation of cells in the G2/M phase of the cell cycle with altered cell morphology including large, poly-nucleated cells. Moreover, ANLN siRNA knockdown also resulted in decreased expression of cyclins D1, A2 and B1.ConclusionsANLN expression in breast cancer cells plays an important role during cell division and a high fraction of nuclear ANLN expression in tumor cells is correlated to poor prognosis in breast cancer patients, independent of Ki-67, tumor size, hormone receptor status, HER2 status, nodal status and age.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2923-8) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 53%

ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer

et al. 2016

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“…23 and Zhou et al . 28 , who reported that ANLN participated in the proliferation and invasion of lung cancer and breast cancer, respectively. As we proved that ANLN-targeting siRNA was effective at inhibiting cancer cell growth and invasion, ANLN might become a candidate target for development of anticancer drugs.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma

Zeng

et al. 2017

Sci Rep

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The prognosis of bladder urothelial carcinoma (BLCA) varies greatly even for patients with similar pathological characteristics. We conducted transcriptome sequencing on ten pairs of BLCA samples and adjacent normal tissues to identify differentially expressed genes. Anillin (ANLN) was identified as a transcript that was significantly up-regulated in BLCA samples compared with normal tissues. Prognostic power of candidate gene was studied using qRT-PCR and immunohistochemistry on 40 and 209 patients, respectively. Patients with elevated ANLN expression level was correlated with poorer cancer-specific (median, 22.4 vs. 37.3 months, p = 0.001), progression-free (median, 19.7 vs. 27.9 months, p = 0.001) and recurrence-free survival (median, 17.1 vs. 25.2 months, p = 0.011) compared with low ANLN expression. Public datasets TCGA and NCBI-GEO were analyzed for external validation. Knockdown of ANLN in J82 and 5637 cells using small interfering RNA significantly inhibited cell proliferation, migration, and invasion ability. Moreover, knockdown of ANLN resulted in G2/M phase arrest and decreased expression of cyclin B1 and D1. Microarray analysis suggested that ANLN played a major role in cell migration and was closely associated with several cancer-related signaling pathways. In conclusion, ANLN was identified as a promising prognostic biomarker which could be used to stratify different risks of BLCA.

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“…NREP and P311) was decreased in nc886 KO (Figure 5). These genes have been reported to inhibit tumor cell proliferation and migration when suppressed [22, 23] and their lower expression was associated with good survival of patients in the TCGA cohort (Figure 5). Therefore, nc886 and some of its associated genes could be an informative marker in deciding the extent of surgery in preoperative settings and in determining the dose of radioactive iodine therapy after surgery to improve the patient's outcome.…”

Section: Discussionmentioning

confidence: 99%

nc886, a non-coding RNA and suppressor of PKR, exerts an oncogenic function in thyroid cancer

et al. 2016

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nc886 is a recently identified cellular non-coding RNA and its depletion leads to acute cell death via PKR (Protein Kinase RNA-activated) activation. nc886 expression is increased in some malignancies, but silenced in others. However, the precise role of nc886/PKR is controversial: is it a tumor suppressor or an oncogene? In this study, we have clarified the role of nc886 in thyroid cancer by sequentially generating PKR knockout (KO) and PKR/nc886 double KO cell lines from Nthy-ori 3-1, a partially transformed thyroid cell line. Compared to the wildtype, PKR KO alone does not exhibit any significant phenotypic changes. However, nc886 KO cells are less proliferative, migratory, and invasive than their parental PKR KO cells. Importantly, the requirement of nc886 in tumor phenotypes is totally independent of PKR. In our microarray data, nc886 KO suppresses some genes whose elevated expression is associated with poor survival confirmed by data from total of 505 thyroid cancer patients in the Caner Genome Atlas project. Also, the nc886 expression level tends to be elevated and in more aggressively metastatic tumor specimens from thyroid cancer patients. In summary, we have discovered nc886's tumor-promoting role in thyroid cancer which has been concealed by the PKR-mediated acute cell death.

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Knockdown of ANLN by lentivirus inhibits cell growth and migration in human breast cancer

Cited by 83 publications

References 26 publications

ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer

ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer

Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma

nc886, a non-coding RNA and suppressor of PKR, exerts an oncogenic function in thyroid cancer

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