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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.


Related in: MedlinePlus

Upregulation of KIAA0101 in ovarian cancer samples. a Relative mRNA levels of KIAA0101 was determined by qRT-PCR in 40 EOC tissues and in 20 normal epithelial tissues samples. P < 0.001. b KIAA0101 expression was determined by western blot in primary and greater omentum metastatic EOC tissues from two patients. c KIAA0101 expression was determined by IHC in primary and greater omentum metastatic EOC tissues. Scale bar 100 µM
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Fig1: Upregulation of KIAA0101 in ovarian cancer samples. a Relative mRNA levels of KIAA0101 was determined by qRT-PCR in 40 EOC tissues and in 20 normal epithelial tissues samples. P < 0.001. b KIAA0101 expression was determined by western blot in primary and greater omentum metastatic EOC tissues from two patients. c KIAA0101 expression was determined by IHC in primary and greater omentum metastatic EOC tissues. Scale bar 100 µM

Mentions: In order to determine the clinical relevance of KIAA0101 in human EOC development, we analyzed the expression levels of KIAA0101 in 40 primary EOC tumor tissues and 20 normal ovarian epithelial tissues. We found that compared to those in normal ovarian epithelial tissues, the levels of KIAA0101 expression were significantly higher in EOC tissues (Fig. 1a, p < 0.001). Cancer cells were found metastasized to the greater omentum in two of those EOC patients. Furthermore, we performed western blot to test KIAA0101 protein expression in primary EOC tissues and two EOC tissues with greater omentum, and found KIAA0101 was significantly higher in metastatic EOC tissues (Fig. 1b). Consistently, IHC results revealed that KIAA0101 staining was stronger in greater omentum metastatic EOC tissues compared to paired primary cancer tissues (Fig. 1c). Taken together, these data indicated that KIAA0101 was up-regulated in EOC tissues, and may play an important role in promoting EOC metastasis.Fig. 1


KIAA0101, a target gene of miR-429, enhances migration and chemoresistance of epithelial ovarian cancer cells
Upregulation of KIAA0101 in ovarian cancer samples. a Relative mRNA levels of KIAA0101 was determined by qRT-PCR in 40 EOC tissues and in 20 normal epithelial tissues samples. P < 0.001. b KIAA0101 expression was determined by western blot in primary and greater omentum metastatic EOC tissues from two patients. c KIAA0101 expression was determined by IHC in primary and greater omentum metastatic EOC tissues. Scale bar 100 µM
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037619&req=5

Fig1: Upregulation of KIAA0101 in ovarian cancer samples. a Relative mRNA levels of KIAA0101 was determined by qRT-PCR in 40 EOC tissues and in 20 normal epithelial tissues samples. P < 0.001. b KIAA0101 expression was determined by western blot in primary and greater omentum metastatic EOC tissues from two patients. c KIAA0101 expression was determined by IHC in primary and greater omentum metastatic EOC tissues. Scale bar 100 µM
Mentions: In order to determine the clinical relevance of KIAA0101 in human EOC development, we analyzed the expression levels of KIAA0101 in 40 primary EOC tumor tissues and 20 normal ovarian epithelial tissues. We found that compared to those in normal ovarian epithelial tissues, the levels of KIAA0101 expression were significantly higher in EOC tissues (Fig. 1a, p < 0.001). Cancer cells were found metastasized to the greater omentum in two of those EOC patients. Furthermore, we performed western blot to test KIAA0101 protein expression in primary EOC tissues and two EOC tissues with greater omentum, and found KIAA0101 was significantly higher in metastatic EOC tissues (Fig. 1b). Consistently, IHC results revealed that KIAA0101 staining was stronger in greater omentum metastatic EOC tissues compared to paired primary cancer tissues (Fig. 1c). Taken together, these data indicated that KIAA0101 was up-regulated in EOC tissues, and may play an important role in promoting EOC metastasis.Fig. 1

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.


Related in: MedlinePlus