siRNA-mediated knockdown of ID1 disrupts Nanog- and Oct-4-mediated cancer stem cell-likeness and resistance to chemotherapy in gastric cancer cells

Abstract

Abstract. DNA-binding protein inhibitor ID-1 (ID1) serves an essential role in tumor progression, and the self-renewal and pluripotency of embryonic stem cells. However, the effect of ID1 on the stemness and cancer stem cell (CSC)-like properties of gastric adenocarcinoma cells remains to be elucidated. In the present study, effective ID1 knockdown was achieved in gastric cancer (GC) cells using small interfering RNA, and the self-renewal ability and cisplatin (DDP) sensitivity of GC cells was subsequently examined. ID1 knockdown in the MKN-28 and MGC-803 cell lines was demonstrated to significantly suppress colony formation (P=0.005 in MKN-28 and P=0.001 in MGC-803), tumor spheroid formation (P=0.021 in MKN-28 and P=0.037 in MGC-803), cell proliferation (P=0.028 in MKN-28 and P=0.001 in MGC-803) and migration (P=0.002 in MKN-28 and P=0.015 in MGC-803). To the best of our knowledge, the present study revealed for the first time that ID1 knockdown suppresses the expression of the key CSC-associated factors Nanog and octamer-binding protein 4 (Oct-4). It was further demonstrated that ID1 knockdown sensitized GC cells to DDP. In conclusion, knockdown of ID1 attenuates the stem cell like-properties of self-renewal in normal GC cells, potentially through the targeting of Nanog and Oct-4, and subsequently decreases cell proliferation and resistance to DDP. The results of the present study suggest that ID1 functions as an oncogene in GC and regulates the stem cell like-properties of gastric cancer cells by targeting Nanog and Oct-4.

Proline-Rich Protein 11 Regulates Self-Renewal and Tumorigenicity of Gastric Cancer Stem Cells

“…The CSCs possess critical roles in gastric cancer initiation, progression, and recurrence associated with resistance to radio-and chemotherapy [18]. In the present study, we showed that PRR11 was highly expressed in a subpopulation of gastric cancer cells with stem-like characteristics, and sat at the center of a signaling network, since changes in its expression pattern could drastically alter the biology properties of gastric CSCs and non-CSCs.…”

Prognostic ability of DNA‑binding protein inhibitor ID‑1 expression in patients with oral squamous cell carcinoma

“…ID-1 plays a number of key roles in cellular differentiation, cell cycle progression, tumorigenesis and metastasis (18). ID-1 predominantly acts as an oncogene in several types of tumor, including gastric (19), pancreatic (20), colorectal (21) and lung cancer (22). Furthermore, a previous study demonstrated that higher protein levels of ID-1 are associated with tumor recurrence and lymph node metastasis in patients with OSCC (11).…”

Engrailed-2 promotes a malignant phenotype of esophageal squamous cell carcinoma through upregulating the expression of pro-oncogenic genes

“…Certain members of the homeobox superfamily have been implicated in normal development as well as in the pathological development of cancer. OCT-4 is a homeobox gene well known for its function in generating induced pluripotent stem cells (Bhartiya, 2013;Seiler et al, 2011); this gene has also been identified as an oncogene known for promoting the features of cancer stem cells (Li et al, 2017;Phiboonchaiyanan & Chanvorachote, 2017). In addition to OCT-4, an increasing body of evidence reveals that homeobox genes may participate in the promotion of various malignant phenotypes such as the proliferation, migration and invasion of cancers (Hirao et al, 2019;Miwa & Kanda, 2019;Rodini et al, 2012;Song et al, 2019).…”