PCNA and JNK1‐Stat3 pathways respectively promotes and inhibits diabetes‐associated centrosome amplification by targeting at the ROCK1/14‐3‐3σ complex in human colon cancer HCT116 cells

Abstract

We have recently reported that type 2 diabetes promotes centrosome amplification via enhancing the expression, biding, and centrosome translocation of rho‐associated coiled‐coil containing protein kinase 1 (ROCK1)/14‐3‐3σ complex in HCT116 cells. In the functional proteomic study, we further investigated the molecular pathways underlying the centrosome amplification using HCT116 cells. We found that treatment of HCT116 cells with high glucose, insulin, and palmitic acid triggered the centrosome amplification and increased the expressions of proliferating cell nuclear antigen (PCNA), nucleophosmin (NPM), and 14‐3‐3σ. Individual knockdown of PCNA, NPM, or 14‐3‐3σ inhibited the centrosome amplification. Knockdown of PCNA inhibited the treatment‐increased expression of ROCK1, whereas knockdown of ROCK1 did not affect the PCNA expression. High glucose, insulin, and palmitic acid also increased the expressions of c‐Jun N‐terminal kinase‐1 (JNK1) and signal transducer and activator of transcription 3 (Stat3), individual knockdown of which upregulated the treatment‐increased expression of 14‐3‐3σ and promoted the centrosome amplification. In contrast, overexpression of JNK1 inhibited the centrosome amplification. Knockdown of Stat3 enhanced the centrosome translocation of 14‐3‐3σ. Moreover, we showed that knockdown of JNK1 inhibited the treatment‐increased expression of Stat3. Knockdown of PCNA, JNK1, or Stat3 did not have an effect on NPM and vice versa. In conclusion, our results suggest that PCNA and JNK1‐Stat3 pathways respectively promotes and feedback inhibits the centrosome amplification by targeting at the ROCK1/14‐3‐3σ complex, and NPM serves as an independent signal for the centrosome amplification.

Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis

“…MMP2, MMP9, PCNA, ROCK1, and ROCK2 were increased in a mouse model of AS, and the receptor antagonist of IL-8, playing a key part in VSMCs proliferation and migration, could suppress the development of AS by inhibiting ROCKs [ 41 ]. Intriguingly, Lu et al [ 42 ] expounded that knockdown of PCNA inhibited ROCK1 expression in colon cancer HCT116 cells, whereas ROCK1 knockdown did not affect PCNA expression. This finding hinted that ROCK1 silence could be downregulating PCNA expression in a content-dependent manner, such as in VSMCs with high ox-LDL level.…”

Identification and validation of 12 immune‐related genes as a prognostic signature for colon adenocarcinoma

“…With its increasing incidence in recent years, a large number of patients have found that the tumor had developed to the advanced stage at the time of diagnosis. [16] Despite the development of modern medical technology, radiotherapy, and chemotherapy, as well as other biological immunotherapy methods, the primary treatment for colon cancer is still largely surgical treatment. However, traditional radical resection of colon cancer fails to achieve ideal effects, which tends to cause recurrence, metastasis, and other problems.…”

The SH2 domain and kinase activity of JAK2 target JAK2 to centrosome and regulate cell growth and centrosome amplification

“…STAT3 is also involved in the regulation of supernumerary centrosome clustering via Stathmin/PLK1 [92]. In contrast, recent data have shown that STAT3 inhibits centrosomal amplification via JNK1 pathway [93], demonstrating that mechanisms responsible for the effect of STATs on centrosomal amplification remain elusive. These issues have not been investigated here, and will be addressed in detail in our planned future studies.…”