Zelin Liu

Heat shock protein family A (HSP70) member 5 (HSPA5) is aberrantly expressed in various tumors and closely associated with the progression and prognosis of cancer. Nevertheless, its role in bladder cancer (BCa) remains elusive. The results of our study demonstrated that HSPA5 was upregulated in BCa and correlated with patient prognosis. Cell lines with low expression level of HSPA5 were constructed to explore the role of this protein in BCa. HSPA5 knockdown promoted apoptosis and retarded the proliferation, migration and invasion of BCa cells by regulating the VEGFA/VEGFR2 signaling pathway. In addition, overexpression of VEGFA alleviated the negative effect of HSPA5 downregulation. Moreover, we found that HSPA5 could inhibit the process of ferroptosis through the P53/SLC7A11/GPX4 pathway. Hence, HSPA5 can facilitate the progression of BCa and may be used as a novel biomarker and latent therapeutic target in the clinic.

Prostate cancer (PCa) is one of the most common cancers and is the second leading cause of mortality in men. Studies exploring novel therapeutic methods are urgently needed. FAM107A, a coding gene located in the short arm of chromosome3, is generally downregulated in PCa and is associated with a poor prognosis. However, the downregulation of FAM107A in PCa and the mechanism of its action remain challenging to determine. This investigation found that downregulation of FAM107A expression in PCa was caused by hypermethylation of CpG islands. Furthermore, DNA methyltransferase 1 (DNMT1) was involved in maintaining hypermethylation. Mechanistically, overexpression of FAM107A inhibits tumor cell proliferation, migration, invasion and promotes apoptosis through the FAK/PI3K/AKT signaling pathway, indicating that FAM107A may be a molecular brake of FAK/PI3K/AKT signaling, thus limiting the active state of the FAK/PI3K/AKT pathway. These findings will contribute to a better understanding of the effect of FAM107A in PCa, and FAM107A may represent a new therapeutic target for PCa.

Background: Prostate cancer (PCa) is a malignancy with high incidence and the principal cause of cancer deaths in men. GATA binding protein 5 (GATA5) belongs to the GATA gene family. GATA5 has a close association with carcinogenesis, but the role of GATA5 in PCa remains poorly understood. The aim of our present study was to probe into the effect of GATA5 on PCa progression and to elucidate the involved mechanism. Methods: The expression of GATA5 was detected in both PCa samples and PCa cell lines. GATA5 overexpression, PLAGL2 knockdown, and overexpression cell models were generated, then Western blotting experiments were utilized to validate the efficiency of transfection. The effects of GATA5 on PCa cell proliferation, metastasis, apoptosis, cell cycle progression, and EMT were detected in vitro or in vivo. Furthermore, the mechanism by which GATA5 inhibits prostate cancer progression through regulating PLAGL2 via the FAK/PI3K/AKT pathway was also explored. Results: GATA5 expression was downregulated in PCa samples and cell lines. GATA5 overexpression inhibited PCa cell proliferation and metastasis but increased the rate of apoptosis. In addition, we confirmed that GATA5 inhibited prostate cancer progression, including EMT, by regulating PLAGL2 via the FAK/PI3K/AKT pathway. Conclusion: We demonstrated that GATA5, as a tumor suppressor in PCa, inhibits PCa progression by regulating PLAGL2. These results showed that the GATA5/PLAGL2/FAK/PI3K/AKT pathway may become a new therapeutic direction for the treatment of PCa.