Sam68 expression and cytoplasmic localization is correlated with lymph node metastasis as well as prognosis in patients with early-stage cervical cancer

Li, Z.; Yu, Chunping; Zhong, Yi; Liu, T. J.; Huang, Qidan; Zhao, Xinge; Huang, Huiqiang; Tu, Hua; Jiang, Shan; Zhang, Yanna; Liu, Jihong; Song, Libing

doi:10.1093/annonc/mdr290

Cited by 68 publications

(75 citation statements)

References 29 publications

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“…It has been reported that high expression of Sam68 is a is a predictor of poor prognosis in non-small cell lung cancer, oral tongue cancer, early-stage cervical cancer and colorectal cancer (8,9,13,14). In the present study, the expression level of Sam68 was demonstrated to be higher in NB tissues compared with their matched adjacent normal tissues.…”

Section: Discussionsupporting

confidence: 54%

MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68

Zhao

Tian

et al. 2015

Molecular Medicine Reports

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Abstract. Neuroblastoma (NB) is the most common solid extracranial tumor in children. However, the molecular mechanism of NB remains to be elucidated. In the present study, reverse transcription quantitative polymerase chain reaction data demonstrated that the expression of Sam68 was significantly upregulated in NB tissues compared with their matched adjacent normal tissues. Furthermore, it was revealed that reduced expression of miR-203 and increased expression of Sam68 co-existed in NB tissues. Knockdown of Sam68 reduced the proliferation, migration and invasion of human SK-N-SH and SH-SY5Y NB cells. Similarly, overexpression of miR-203 also inhibited the proliferation, migration and invasion of these two cell lines. It was further demonstrated that the protein expression level of Sam68 was negatively mediated by miR-203 in the SK-N-SH and SH-SY5Y NB cells. Additionally, data from a dual luciferase reporter assay confirmed that miR-203 directly targeted Sam68 by binding to its 3'-untranslated region. In conclusion, the present study suggested for the first time, to the best of our knowledge, that the aberrant downregulation of miR-203 may contribute to the aberrant upregulation of Sam68 in NB and that miR-203 has an inhibitory role in malignant progression of NB by targeting Sam68. The present study provided evidence to support miR-203/Sam68 as a novel diagnostic or therapeutic targets for NB.

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Section: Discussionsupporting

confidence: 54%

MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68

Zhao

Tian

et al. 2015

Molecular Medicine Reports

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“…Sam68 expression in cervical cancer was significantly upregulated. It was found that Sam68 could induce cervical cancer lymph node metastasis, which served as predictors of pelvic lymph node metastasis in cervical cancer patients [25]. In the colorectal cancer tissues, Sam68 was also elevated, and the high Sam68 expression level was significantly correlated with the characteristics of aggressive colorectal cancer [26].…”

Section: Discussionmentioning

confidence: 98%

“…There are numerous circumstances that activation of various receptor systems, such as leptin and insulin receptors, results in tyrosine phosphorylation of Sam68 that regulate the subcellular localization. In cervical cancer [25], Sam68 may be regulated by posttranslational modifications to localize to the cytoplasm where Sam68 interacts with PI3K and induces lymph node metastasis through Akt/GSK-3b/Snail pathway-mediated EMT. Sam68 cytoplasmic localizations were predictors of poor survival.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of Sam68 expression in endometrial carcinoma

Liu

Qin

et al. 2015

Tumor Biol.

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Sam68 (Src-associated in mitosis of 68 kDa) is a substrate for tyrosine kinase c-Src during mitosis. The nuclear protein level has been found to be associated with progression and prognosis in various human malignant tumors. The aim of this study is to investigate the clinical value of Sam68 in endometrial carcinoma (EC). Sam68 expression was confirmed by real-time PCR, Western blot, and immunofluorescent assay in primary normal endometrial epithelial cells, endometrial carcinoma cell lines, as well as seven pairs of EC and matched adjacent noncancerous endometrial tissues. Moreover, the protein level of Sam68 was evaluated by immunohistochemistry in a cohort of surgical specimens derived from 131 patients including primary endometrial carcinoma (n = 95), endometrial atypical hyperplasia (precancerous lesions, n = 26), and normal endometria (n = 10). In endometrial cancer cell lines, RNA interfering approach was employed to downregulate Sam68 expression to determine its role in proliferation. Clinicopathological relevance and prognostic associations were examined by statistical analyses. Compared with normal endometrial and endometrial atypical hyperplasia tissues, Sam68 significantly elevated in endometrial cancer samples (P < 0.01), which was negative or low in 37 cases (38.9 %) and high in 58 cases (61.1 %). The high expression of Sam68 was associated with histological grade (P < 0.001), FIGO stage (P = 0.039), and myometrial invasion (P = 0.002). Kaplan-Meier analysis demonstrated that overexpression of Sam68 correlated with shorter overall survival. It is confirmed by univariate and multivariate analysis (P < 0.001 and P = 0.048, respectively). Additionally, we found that Sam68 was highly expressed at both the transcriptional and translational levels in endometrial cancer cell lines (Ishikawa, HEC-1B, AN3CA, KLE, and RL95-2) and siRNA knockdown of Sam68 remarkably inhibited cellular proliferation in in vitro models. Sam68 may be useful prognostic marker for EC, and it plays an important role in promoting the cellular proliferation. Further investigation of Sam68 as a potential therapeutic target for EC patients could be of interest.

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“…The results above indicated that the molecular mechanism of Sam68 downregulation was closely related to the induction of p21 Cip1 and p27 Kip1 and the reduction of p-Rb in ESCC cells. Some evidences displayed that Sam68 reduction decreased the expression of p-Akt and p-GSK-3β in breast cancer cells [8] and cervical cancer cells [10]. Yet little is known about the relationship of Sam68 and the Akt/GSK-3β pathway in ESCC.…”

Section: Sam68 Knock Down Promotes Cell Proliferation In Escc Cellsmentioning

confidence: 99%

“…It was found that the expression of Sam68 was correlated with glioblastoma [6], breast cancer [8], prostate cancer [9], and cervical Yayun Wang and Li Liang contributed equally to this work. cancer [10]. What is more, further research found that the cell cycle disorder controlled by Sam68 played an important role in tumorigenesis.…”

Section: Introductionmentioning

confidence: 96%

Sam68 promotes cellular proliferation and predicts poor prognosis in esophageal squamous cell carcinoma

Wang

Zhang

et al. 2015

Tumor Biol.

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Sam68 (Src-associated in mitosis of 68 kD) is a KH domain RNA-binding protein. The expression of Sam68 was correlated with kinds of tumors. Yet, the expression mechanisms and physiological significance of Sam68 in ESCC remains unclear. In this study, we clarified a potential role of Sam68 in the treatment of ESCC. Western blot and immunohistochemistry (IHC) analysis revealed that the protein level of Sam68 was higher in ESCC tumor tissues and cell lines. In addition, IHC stain revealed that Sam68 was positively correlated with clinical pathologic variables such as tumor grade and tumor invasion. In addition, Sam68 could be an independent prognostic indicator for patients' overall survival. In vitro studies such as starvation and refeeding assay along with Sam68-shRNA transfection assay demonstrated that Sam68 expression promoted proliferation of ESCC cells. And Sam68 downregulation caused decreased rate of cell growth and colony formation. Reasons are associated with growth arrest of cell cycle at G1/S phase. Moreover, our results clarified that Sam68 could promote ESCC cell proliferation via the activation of Akt/GSK-3β pathway. This research indicated that Sam68 might accelerate the cell cycle progression and be considered as a new therapy target in ESCC.

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Sam68 expression and cytoplasmic localization is correlated with lymph node metastasis as well as prognosis in patients with early-stage cervical cancer

Cited by 68 publications

References 29 publications

MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68

MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68

Clinical significance of Sam68 expression in endometrial carcinoma

Sam68 promotes cellular proliferation and predicts poor prognosis in esophageal squamous cell carcinoma

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