Shan Li

The interaction between PDCD4 and YB1 is critical for cervical cancer stemness and cisplatin resistance

AbstractCancer multidrug resistance (MDR) is existence in stem cell‐like cancer cells characterized by stemness including high‐proliferation and self‐renewal. Programmed cell death 4 (PDCD4), as a proapoptotic gene, whether it engaged in cancer stemness and cisplatin resistance is still unknown. Here we showed that PDCD4 expressions in Hela/DDP (cisplatin resistance) cells were lower than in parental Hela cells. Moreover, the levels of drug resistance genes and typical stemness markers were markedly elevated in Hela/DDP cells. In vivo, xenograft tumor assay confirmed that knockdown of PDCD4 accelerated the grafted tumor growth. In vitro, colony formation and MTT assay demonstrated that PDCD4 overexpression inhibited cells proliferation in conditions with or without cisplatin. By contrast, PDCD4 deficiency provoked cell proliferation and cisplatin resistance. On mechanism, PDCD4 decreased the protein levels of pAKT and pYB1, accompanied by reduced MDR1 expression. Correspondingly, luciferase reporter assay showed PDCD4 regulated MDR1 promoter activity entirely relied on YB1. Furthermore, Ch‐IP, GST‐pulldown, and Co‐IP assays provided novel evidence that PDCD4 could directly bind with YB1 by the nucleolar localization signal (NOLS) segment, causing the reduced YB1 binding into the MDR1 promoter region through blocking YB1 nucleus translocation, triggering the decreased MDR1 transcription. Taken together, PDCD4‐pAKT‐pYB1 forms the integrated molecular network to regulate MDR1 transcription during the process of stemness‐associated cisplatin resistance.

Diagnostic Value of Albumin to Fibrinogen Ratio in Cervical Cancer

Background: Albumin to fibrinogen ratio (AFR) play a crucial role in the progression and prognosis of many malignant tumors. This study aimed to comprehensively assess the diagnostic value of AFR as single markers or in combination with squamous cell carcinoma antigen (SCC-Ag), cancer antigen 125 (CA-125) in cervical cancer. Methods: A total of 323 cervical cancer inpatients, 143 patients with cervical intraepithelial neoplasia (CIN) and 317 healthy controls were analyzed. Differences in laboratory parameters and clinicopathological features were calculated using the Mann–Whitney U or Kruskal–Wallis H test. The receiver operating characteristic (ROC) curve was used to evaluate the predicted value of AFR, alone or combined with SCC-Ag, CA-125 for the diagnosis of cervical cancer. Results: The levels of AFR in patients with cervical cancer were significantly lower than those in the CIN patients and the control subjects. AFR were not only negatively correlated with the tumor stage, but also related to histology typing, lymph node metastasis, distant metastasis, depth of stromal infiltration, tumor size, and tumor stage; however, it was not associated with the blood group. AFR combined with SCC-Ag possessed a larger area under the curve (AUC; AUCAFR+SCC-Ag = 0.924, 95% confidence interval (CI) 0.900, 0.944) than AFR ( P < 0.001), SCC-Ag ( P < 0.001), or CA-125 ( P < 0.001) did alone. Conclusions: The pretreatment levels of AFR, alone or combined with SCC-Ag, CA-125 could improve the diagnostic efficiency of cervical cancer.

Upregulation of SOX9 promotes the self‐renewal and tumorigenicity of cervical cancer through activating the Wnt/β‐catenin signaling pathway

Abstract Sry‐box9 (SOX9) maintains stem cell properties and plays crucial roles in many cancers. However, whether SOX9 is correlated with cervical cancer cell stemness and its detailed mechanism remains obscure. We studied the relationship between SOX9 and prognosis of cervical cancer through public database, and SOX9 was related to poor prognosis of cervical cancer. Elevated SOX9 expression enhanced the self‐renewal properties and promotes tumorigenicity in cervical cancer. Overexpression of SOX9 could promote the expression of stem cell‐related factors in cervical cancer cells and xenografts. Meanwhile, overexpression of SOX9 could also enhance the expressions of FZD10, β‐catenin, and c‐Myc in cervical cancer cells and xenografts, while inhibiting the expression of DDK1. The activation of Wnt pathway by chir‐99 021 raised the tumor spheroid ability of SOX9 knockdown HeLa cells. In addition, SOX9 could transcriptional inhibit DKK1 and activate FZD10 and MYC by binding to their promoters to affect the Wnt/β‐catenin pathway. These results demonstrated SOX9 regulated the self‐renewal and tumorigenicity of cervical cancer through Wnt/β‐catenin pathway by directly transcriptional activation of FZD10, MYC and transcriptional inhibition of DKK1.