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KIAA0101, a target gene of miR-429, enhances migration and chemoresistance of epithelial ovarian cancer cells

View Article: PubMed Central - PubMed

ABSTRACT

Background: Ovarian cancer is a common type of gynecological malignancies, and is the fifth leading cause of cancer-related death in women in the United States. MiR-429 and KIAA0101 have been found to be involved in several human malignancies, respectively. However, the role of miR-429 and KIAA0101, and the correlation between them during development of epithelial ovarian cancer (EOC) remain to be investigated.

Methods: The expression of KIAA0101 in EOC tissues and cells was measured by Quantitative real-time PCR, western blot, and immunochemistry. Cell proliferation assay, colony formation assay, and transwell assay was performed to assess the role of miR-429 and KIAA0101 in regulation of proliferation, migration, and chemoresistance of EOC cells. Luciferase assay was used to test the Wnt/β-catenin signaling activity in response to depletion of KIAA0101 and overexpression of miR-429.

Results: We found that KIAA0101 was upregulated in metastatic EOC tissues, compared to primary EOC tissues, and KIAA0101 was required for the migration activity and chemoresistance of EOC cells by enhancing Wnt/β-catenin signaling. Furthermore, we revealed KIAA0101 is direct target of miR-429. Similar to knockdown of KIAA0101, overexpression of miR-429 reduced invasion and chemoresistance of EOC cells. Co-transfection of KIAA0101 partially abrogates the inhibitory effects on invasion and chemoresistance in EOC cells.

Conclusions: KIAA0101, a target gene of miR-429, was upregulated in the metastatic EOC tissues, and enhanced the migration activity and chemoresistance of EOC cells. Both miR-429 and KIAA0101 may represent the potential therapeutic targets of EOC.

No MeSH data available.


KIAA0101 regulates Wnt/β-catenin signaling in EOC cells. a Luciferase activities in SKOV3 and COV644 cells 48 h after co-transfection with TOP flash luciferase plasmid and siR-KIAA0101 or siR-Control. b Levels of β-catenin was determined by Western blot in nucleus and cytoplasm of SKOV3 and COV644 cells transfected with siR-KIAA0101 or siR-Control. c mRNA and d protein levels of Axin2 and c-myc in SKOV3 and COV644 cells transfected with siR-KIAA0101 or siR-Control. *p < 0.05 compared with siR-Control transfected cells
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Fig4: KIAA0101 regulates Wnt/β-catenin signaling in EOC cells. a Luciferase activities in SKOV3 and COV644 cells 48 h after co-transfection with TOP flash luciferase plasmid and siR-KIAA0101 or siR-Control. b Levels of β-catenin was determined by Western blot in nucleus and cytoplasm of SKOV3 and COV644 cells transfected with siR-KIAA0101 or siR-Control. c mRNA and d protein levels of Axin2 and c-myc in SKOV3 and COV644 cells transfected with siR-KIAA0101 or siR-Control. *p < 0.05 compared with siR-Control transfected cells

Mentions: KIAA0101 regulates Wnt/β-catenin signaling in colon cancer cells [25]. In order to elucidate the molecular mechanisms of KIAA0101′s function in EOC, TOP flash reporter luciferase assays revealed the Wnt/β-catenin signaling activity was inhibited by depletion of KIAA0101 (Fig. 4a). We then examined β-catenin levels in the nucleus and cytoplasm of SKOV3 and COV644 cells in response to KIAA0101 silencing. The result showed that depletion of KIAA0101 inhibited β-catenin nuclear translocation (Fig. 4b). Furthermore, we performed qRT-PCR and western blot to investigate the expression of Wnt/β-catenin signaling downstream genes, Axin2 and c-myc. Consistently, the expression of Axin2 and c-myc was decreased after knockdown of KIAA0101 (Fig. 4c, d). These findings provided the evidences that KIAA0101 regulates Wnt/β-catenin signaling.Fig. 4


KIAA0101, a target gene of miR-429, enhances migration and chemoresistance of epithelial ovarian cancer cells
KIAA0101 regulates Wnt/β-catenin signaling in EOC cells. a Luciferase activities in SKOV3 and COV644 cells 48 h after co-transfection with TOP flash luciferase plasmid and siR-KIAA0101 or siR-Control. b Levels of β-catenin was determined by Western blot in nucleus and cytoplasm of SKOV3 and COV644 cells transfected with siR-KIAA0101 or siR-Control. c mRNA and d protein levels of Axin2 and c-myc in SKOV3 and COV644 cells transfected with siR-KIAA0101 or siR-Control. *p < 0.05 compared with siR-Control transfected cells
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037619&req=5

Fig4: KIAA0101 regulates Wnt/β-catenin signaling in EOC cells. a Luciferase activities in SKOV3 and COV644 cells 48 h after co-transfection with TOP flash luciferase plasmid and siR-KIAA0101 or siR-Control. b Levels of β-catenin was determined by Western blot in nucleus and cytoplasm of SKOV3 and COV644 cells transfected with siR-KIAA0101 or siR-Control. c mRNA and d protein levels of Axin2 and c-myc in SKOV3 and COV644 cells transfected with siR-KIAA0101 or siR-Control. *p < 0.05 compared with siR-Control transfected cells
Mentions: KIAA0101 regulates Wnt/β-catenin signaling in colon cancer cells [25]. In order to elucidate the molecular mechanisms of KIAA0101′s function in EOC, TOP flash reporter luciferase assays revealed the Wnt/β-catenin signaling activity was inhibited by depletion of KIAA0101 (Fig. 4a). We then examined β-catenin levels in the nucleus and cytoplasm of SKOV3 and COV644 cells in response to KIAA0101 silencing. The result showed that depletion of KIAA0101 inhibited β-catenin nuclear translocation (Fig. 4b). Furthermore, we performed qRT-PCR and western blot to investigate the expression of Wnt/β-catenin signaling downstream genes, Axin2 and c-myc. Consistently, the expression of Axin2 and c-myc was decreased after knockdown of KIAA0101 (Fig. 4c, d). These findings provided the evidences that KIAA0101 regulates Wnt/β-catenin signaling.Fig. 4

View Article: PubMed Central - PubMed

ABSTRACT

Background: Ovarian cancer is a common type of gynecological malignancies, and is the fifth leading cause of cancer-related death in women in the United States. MiR-429 and KIAA0101 have been found to be involved in several human malignancies, respectively. However, the role of miR-429 and KIAA0101, and the correlation between them during development of epithelial ovarian cancer (EOC) remain to be investigated.

Methods: The expression of KIAA0101 in EOC tissues and cells was measured by Quantitative real-time PCR, western blot, and immunochemistry. Cell proliferation assay, colony formation assay, and transwell assay was performed to assess the role of miR-429 and KIAA0101 in regulation of proliferation, migration, and chemoresistance of EOC cells. Luciferase assay was used to test the Wnt/&beta;-catenin signaling activity in response to depletion of KIAA0101 and overexpression of miR-429.

Results: We found that KIAA0101 was upregulated in metastatic EOC tissues, compared to primary EOC tissues, and KIAA0101 was required for the migration activity and chemoresistance of EOC cells by enhancing Wnt/&beta;-catenin signaling. Furthermore, we revealed KIAA0101 is direct target of miR-429. Similar to knockdown of KIAA0101, overexpression of miR-429 reduced invasion and chemoresistance of EOC cells. Co-transfection of KIAA0101 partially abrogates the inhibitory effects on invasion and chemoresistance in EOC cells.

Conclusions: KIAA0101, a target gene of miR-429, was upregulated in the metastatic EOC tissues, and enhanced the migration activity and chemoresistance of EOC cells. Both miR-429 and KIAA0101 may represent the potential therapeutic targets of EOC.

No MeSH data available.