Metastasis-Associated in Colon Cancer-1 Associates With Poor Prognosis and Promotes Cell Invasion and Angiogenesis in Human Cervical Cancer

Zhou, Xiang; Xu, Changjuan; Wang, Junxian; Dai, Ting; Ye, Yaping; Cui, Yejia; Liao, Wenting; Wu, Xin; Ou, Jianping

doi:10.1097/igc.0000000000000524

Cited by 28 publications

(36 citation statements)

References 41 publications

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“…Invasion and distant metastasis are important events that affect the prognosis and treatment of cervical cancer patients (28). Patients in the later stages of cervical cancer with invasion or metastasis have a significantly worse prognosis (29).…”

Section: Discussionmentioning

confidence: 99%

Lipid raft localization of epidermal growth factor receptor alters matrix metalloproteinase-1 expression in SiHa cells via the MAPK/ERK signaling pathway

Zhang

Wang

et al. 2016

Oncology Letters

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Matrix metalloproteinase-1 (MMP-1) has been identified as an important participant in tumor invasion, metastasis and angiogenesis. The purpose of the present study was to investigate the effects of epidermal growth factor receptor (EGFR) localization to lipid rafts on signaling pathways involved in the regulation of MMP-1 expression in SiHa cells, a cervical cancer cell line. EGFR activation by EGF specifically induced MMP-1 expression at both the messenger RNA and protein levels. Additionally, it was observed that EGFR localized to lipid rafts, and that the redistribution of EGFR induced by lipid raft disruption strengthened EGF-induced MMP-1 expression. MMP-1 induction was blocked by the mitogen-activated protein kinase (MAPK) kinase inhibitors PD98059 and U0126. Our results suggested that lipid rafts provide a platform to inhibit EGFR regulation of MMP-1 in SiHa cells through the MAPK/extracellular signal-regulated kinase signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Lipid raft localization of epidermal growth factor receptor alters matrix metalloproteinase-1 expression in SiHa cells via the MAPK/ERK signaling pathway

Zhang

Wang

et al. 2016

Oncology Letters

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“…MACC1 (Fig. 3A) was predicted as a candidate target of miR-485 and was selected as the focus of the present study, as it has been implicated in the occurrence and development of cervical cancer (23)(24)(25)(26)(27). To confirm this hypothesis, a luciferase reporter assay was performed to confirm the binding of miR-485 to the 3'-UTR of MACC1.…”

Section: Mir-485 Is Underexpressed In Cervical Cancer Tissues and Celmentioning

confidence: 97%

MicroRNA‑485 targets MACC1 and inhibits cervical cancer cell proliferation and invasion

et al. 2018

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A large body of evidence has indicated that microRNAs (miRNAs/miRs) have essential roles in the development and progression of cervical cancer. Thus, miRNAs with dysregulated expression are potential biomarkers for cervical cancer diagnosis and prognosis. In the present study, expression levels of miR‑485 were detected in cervical cancer tissues and cell lines. The effects of miR‑485 overexpression on the proliferation and invasion of cervical cancer cells were determined with Cell Counting kit‑8 and Transwell invasion assays. The mechanisms underlying the action of miR‑485 in cervical cancer were investigated using bioinformatics analysis, a luciferase reporter assay, reverse transcription‑quantitative polymerase chain reaction and western blot analysis. In addition, the association between miR‑485 and metastasis associated in colon cancer‑1 (MACC1) in cervical cancer tissues was examined. The present study demonstrated that miR‑485 expression was significantly downregulated in cervical cancer tissues and cell lines. Reduced miR‑485 expression in patients with cervical cancer was correlated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Furthermore, restored expression of miR‑485 significantly reduced cervical cancer cell proliferation and invasion. MACC1 was identified as a direct target gene of miR‑485 in cervical cancer. MACC1 expression was significantly upregulated in cervical cancer specimens and was inversely correlated with miR‑485 expression. Additionally, the restored expression of MACC1 eliminated the suppressive effects of miR‑485 overexpression on the proliferation and invasion of cervical cancer cells. Notably, the upregulation of miR‑485 suppressed the MET proto‑oncogene, receptor tyrosine kinase (Met)/RAC‑α serine/threonine‑protein kinase (AKT) signaling pathway. These results demonstrated that miR‑485 may perform its tumor suppressive function in cervical cancer by directly targeting MACC1 and inhibiting the Met/AKT signaling pathway. Therefore, the miR‑485/MACC1 axis may be a novel and effective therapeutic target in cervical cancer.

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“…MACC1 was also observed as highly expressed in cervical cancer tissues and cell lines. Increased MACC1 expression levels were significantly correlated with the FIGO stage, pelvic lymph node metastasis and recurrence (20,21). Patients with cervical cancer with high MACC1 expression levels exhibited shorter overall survival times than those patients with low MACC1 expression (21).…”

Section: Discussionmentioning

confidence: 99%

“…3A). MACC1 was selected for further identification as this gene has been widely reported as implicated in cervical cancer carcinogenesis and progression (20)(21)(22)(23)(24)(25). Luciferase reporter assay was applied to confirm whether the 3'-UTR of MACC1 could be directly targeted by miR-877 in cervical cancer cells.…”

Section: Mir-877 Inhibits Macc1 Expression By Directly Targeting Its mentioning

confidence: 99%

MicroRNA‑877 is downregulated in cervical cancer and directly targets MACC1 to inhibit cell proliferation and invasion

et al. 2019

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Previously, a number of microRNAs (miRNAs) have been reported to be dysregulated in cervical cancer, and dysregulated miRNAs may play crucial roles in the development and progression of cervical cancer. Hence, investigating the detailed roles of miRNAs that are aberrantly expressed in cervical cancer and the underlying molecular mechanisms is essential for early diagnosis and effective therapeutic approaches. miRNA-877 (miR-877) was found to be downregulated in hepatocellular carcinoma and renal cell carcinoma, and function as a tumor-suppressive miRNA. However, how miR-877 exerts an effect in cervical cancer progression and its underlying molecular mechanisms remains to be elucidated. In the current study, reverse transcription-quantitative PCR was performed to determine miR-877 expression in cervical cancer tissues and cell lines. The effects of miR-877 overexpression on cervical cancer cell proliferation and invasion were evaluated using MTT and Transwell cell invasion assays. In the present study, miR-877 was significantly downregulated in cervical cancer tissues and cell lines, and the decreased expression levels of miR-877 were significantly associated with increased International Federation of Gynecology and Obstetric stage as well as increased lymph node metastasis in patients with cervical cancer. Upregulation of miR-877 using miR-877 mimics resulted in the decreased proliferation and invasion of cervical cancer cells. Metastasis-associated in colon cancer-1 (MACC1) was assessed using bioinformatics analyses to determine whether it could be a potential target gene of miR-877, and the results were confirmed using a luciferase reporter assay. Furthermore, MACC1 was markedly upregulated in cervical cancer tissues, and its level was negatively correlated with the miR-877 level. Overexpression of miR-877 resulted in decreased expression levels of MACC1 in cervical cancer cells at both the mRNA and protein levels. In addition, the functional effects of MACC1 knockdown were similar to those induced by upregulated miR-877 in cervical cancer cells. MACC1 restored miR-877 overexpression-mediated suppression of cervical cancer cell proliferation and invasion. In conclusion, miR-877 may play an antitumor role in cervical cancer by directly targeting MACC1, which suggests that this miRNA may be a promising therapeutic target for the treatment of patients with such an aggressive gynecological cancer.

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Metastasis-Associated in Colon Cancer-1 Associates With Poor Prognosis and Promotes Cell Invasion and Angiogenesis in Human Cervical Cancer

Abstract: Supplemental digital content is available in the text.

Cited by 28 publications

References 41 publications

Lipid raft localization of epidermal growth factor receptor alters matrix metalloproteinase-1 expression in SiHa cells via the MAPK/ERK signaling pathway

Lipid raft localization of epidermal growth factor receptor alters matrix metalloproteinase-1 expression in SiHa cells via the MAPK/ERK signaling pathway

MicroRNA‑485 targets MACC1 and inhibits cervical cancer cell proliferation and invasion

MicroRNA‑877 is downregulated in cervical cancer and directly targets MACC1 to inhibit cell proliferation and invasion

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