P4HB knockdown induces human HT29 colon cancer cell apoptosis through the generation of reactive oxygen species and inactivation of STAT3 signaling

Abstract

Colon cancer is the second most lethal malignancy worldwide. A better understanding of colon cancer at the molecular level may increase overall survival rates. Previous studies have indicated that prolyl 4-hydroxylase, β polypeptide (P4HB) is associated with tumorigenesis in colon cancer; however, its role and molecular mechanisms in colon cancer remain unclear. In the present study, the cellular responses to P4HB in human colon cancer cell lines were investigated by proliferation and apoptosis assays, western blotting, and immunohistochemistry. The results showed that expression of P4HB was higher in colon cancer tissues compared within adjacent normal tissues. P4HB knockdown increased the apoptosis of human HT29 cells. Furthermore, P4HB knockdown reduced the activation of signal transducer and activator of transcription 3 (STAT3) and promoted accumulation of reactive oxygen species (ROS). Inhibiting the accumulation of ROS abrogated the increased cell apoptosis induced by P4HB knockdown. Notably, decreased ROS levels effectively antagonized the effects of P4HB on STAT3 inactivation. In conclusion, these findings suggested that P4HB knockdown may induce HT29 human colon cancer cell apoptosis through the generation of ROS and inactivation of the STAT3 signaling pathway.

Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastric Cancer

“…as the archetype PDI protein, the chaperone activity of who is independent of catalytic activity, while the former is vital for many client proteins [27]. There is su cient evidence supporting that PDIA1 high expressed in a wide variety of cancers tissues [9][10][11]24] and cancer cells [28]. And the upregulated PDIA1 is closely correlated with cancer metastasis and invasiveness [27].…”

“…Prolyl 4-hydroxylase, beta polypeptide (P4HB, also known as PDIA1) belongs to protein disul de isomerase (PDI) family, close connects with ER stress and UPR, as an enzymatic molecular chaperone to reconstruct misfolded proteins [9]. P4HB is proved to be upregulated in a variety of cancers, such as lung cancer [10], diffuse glioma [9], colon cancer [11]. As a result, P4HB has been reported by numerous researches to be a potential target for cancer therapy [12][13][14].…”

Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastric Cancer

“…P4HB, also known as PDIA1 (usually referred as PDI), as the archetype PDI protein, the chaperone activity of whom is independent of catalytic activity, is vital for many client proteins [27]. There is su cient evidence supporting that PDIA1 high expressed in a wide variety of cancers tissues [9][10][11]24] and cancer cells [28], the upregulated PDIA1 is close correlated with cancer metastasis and invasiveness [27].…”

“…Prolyl 4-hydroxylase, beta polypeptide (P4HB, also known as PDIA1) belongs to protein disul de isomerase (PDI) family, as an enzymatic molecular chaperone to reconstruct misfolded proteins, close connects with ER stress and UPR [9]. P4HB is proved to be upregulated in a variety of cancers, such as diffuse glioma [9], lung cancer [10], and colon cancer [11]. As a result, P4HB has been reported by numerous researches to be a potential target for cancer therapy [12][13][14].…”

Clinic correlation and prognostic value of P4HB and GRP78 expression in gastric cancer

“…P4HB, also known as PDIA1 (usually referred as PDI), as the archetype PDI protein, the chaperone activity of who is independent of catalytic activity, while the former is vital for many client proteins [27]. There is su cient evidence supporting that PDIA1 high expressed in a wide variety of cancers tissues [9][10][11]24] and cancer cells [28]. And the upregulated PDIA1 is closely correlated with cancer metastasis and invasiveness [27].…”