<p>GRHL2 Upregulation Predicts a Poor Prognosis and Promotes the Resistance of Serous Ovarian Cancer to Cisplatin</p>

Abstract

Background: GRHL2 has been shown to function in ovarian carcinogenesis. However, the relationship between GRHL2 and cisplatin (DDP) resistance in serous ovarian cancer (SOC) is not clear. The purpose of this study was to elucidate the function and mechanism of GRHL2 in DDP resistance of SOC. Materials and Methods: Immunohistochemistry (IHC) was utilized to identify GRHL2 protein expression in DDP resistant and sensitive SOC tissues. GRHL2 mRNA and protein levels were identified using quantitative real-time PCR (qRT-PCR) and Western blotting in SKOV3/DDP and SKOV3 cell lines. We conducted loss-and gain-of-function experiments to uncover the consequence of GRHL2 knockdown or overexpression on the sensitivity of ovarian cancer cells to DDP in vitro and in vivo and the underlying mechanism. Results: It was observed that expression of GRHL2 was higher in DDP resistant SOC tissues relative to DDP sensitive SOC tissues. In addition, the increased expression of GRHL2 led to shorter progression-free survival (PFS) and overall survival (OS). Meanwhile, the GRHL2 transcript and protein levels in SKOV3/DDP were also higher than SKOV3. Small hairpin RNA (shRNA)-facilitated GRHL2 gene knockdown considerably heightened the sensitivity of SKOV3/DDP cells to DDP by inhibiting proliferation and promoting apoptosis, while upregulation of GRHL2 significantly reduced the sensitivity of SKOV3 cells to DDP by promoting proliferation and decreasing apoptosis. In addition, GRHL2 promotes DDP resistance of SOC through activation of ERK/MAPK signaling pathways. Conclusion: Our results suggest that GRHL2 up-regulation predicts a poor prognosis and promotes the resistance of SOC to DDP. Therefore, GRHL2 may be a possible treatment target for cisplatin-resistant serous ovarian cancer.

Telomere-related genes as potential biomarkers to predict endometriosis and immune response: Development of a machine learning-based risk model

“…GRHL2 is involved in EMT through CLDN4 core promoter and E-cadherin gene regulation ( 45 ). Gynecological tumor studies have also demonstrated that increased GRHL2 expression is associated with poor prognosis in ovarian cancer ( 46 ). RARRES2 is a small, secreted protein associated with a variety of cancers, and higher serum RARRES2 levels have been shown to be associated with improved overall survival in adrenocortical tumors ( P = 0.0227) ( 47 ).…”

LINC00184 Promotes Ovarian Cancer Cells Proliferation and Cisplatin Resistance by Elevating CNTN1 Expression via Sponging miR-1305

“…Sensitive and resistant patients were defined as follows: patients who developed progressive disease within 6 months after initial treatment were defined as cisplatin resistant; the other patients were defined as cisplatin sensitive. 14 Adjacent normal tissues served as the N group (n=70). Tumor tissues obtained from cisplatin-resistant patients were used as the R group (n=38).…”

Lemur tyrosine kinase-3 (LMTK3) induces chemoresistance to cetuximab in colorectal cancer via the ERK/MAPK pathway

“…Previous reports revealed that ERK/MAPK actively participated in the development of chemoresistance to multiple drugs during chemotherapy for human cancers [24][25][26]. Besides, Raghav et al elucidated the ERK/MAPK pathway activated by HGF/MET axis could animate oncogenic signaling in CTX-resistant tumors to further aggravate chemoresistance [27], indicating that ERK/MAPK signaling contributed to CTX resistance in tumors.…”