Upregulation of miR-125b is associated with poor prognosis and trastuzumab resistance in HER2-positive gastric cancer

Abstract

Gastric cancer is one of the most common types of human cancer associated with a poor prognosis. MicroRNAs (miRs), a class of non-coding RNAs that are 18–25 nucleotides in length, act as key regulators in gene expression, and have been implicated in various human cancer types. miR-125b has been implicated in the malignant progression of gastric cancer. However, the association between miR-125b expression, clinicopathological characteristics and trastuzumab resistance in human epidermal growth factor receptor 2 (HER2)-positive gastric cancer remains unclear. In the current study, in situ hybridization data demonstrated that 81.8% (108/132) of gastric cancer tissues exhibited positive expression of miR-125b, while only 26.3% (10/38) of non-tumor gastric tissues were miR-125b-positive. Reverse transcription-quantitative polymerase chain reaction data indicated that the expression level of miR-125b was markedly increased in gastric cancer tissues compared with non-cancerous gastric tissues. Furthermore, the miR-125b level was significantly associated with tumor (T) stage, lymph node metastasis, distant metastasis and TNM stage of gastric cancer (P<0.05). Increased miR-125b expression predicated poor prognosis in patients with gastric cancer. For HER2-positive gastric cancer, the upregulation of miR-125b expression was significantly associated with advanced malignant progression, as well as a poor prognosis (P<0.05). Furthermore, data from the present study indicated that the increased miR-125b level was significantly associated with trastuzumab resistance in HER2-positive gastric cancer (P<0.05). Therefore, the current study suggests that miR-125b may become a potential biomarker for predicting prognoses and clinical outcomes in patients with HER2-positive gastric cancer that receive trastuzumab treatment.

Dynamics of circulating microRNAs as a novel indicator of clinical response to neoadjuvant chemotherapy in breast cancer

“…We also compared our findings to studies evaluating miRNAs as predictive biomarkers in other types of cancers. In HER2‐positive gastric cancer, Sui et al has demonstrated that increased miR‐125b level in tumor tissue was significantly associated with trastuzumab resistance, advanced malignant progression, as well as poor prognosis. In vitro studies revealed that miR‐21/PTEN and miR‐223/FBXW7 pathways might be implicated in sensitivity of gastric cancer to trastuzumab .…”

A microRNA-4516 inhibitor sensitizes chemo-resistant gastric cancer cells to chemotherapy by upregulating ING4

“…7 Some experiments have shown that certain miRNAs, including miR-25, miR-20a, and miR-623 are associated with a poor prognosis of cancer and have been reported to be signicantly upregulated in recurrent gastric carcinoma. [8][9][10][11][12] Therefore, we hypothesized that gastric cancer resistance may be related to abnormal expression of miRNAs. In addition, a lot of evidence has revealed that miRNA is involved in gastric cancer initiation and progression, including MDR.…”

Noncoding RNAs in gastric cancer: implications for drug resistance

“…Through inhibiting PTEN expression, oncogenic miR-21 has been found to confer trastuzumab resistance in HER2-positive gastric cancer cells [154]. MiR-125b, which is markedly upregulated in gastric cancer tissues, is significantly associated with trastuzumab resistance and poor prognosis in HER2-positive gastric cancer patients [155]. Similarly, oncogenic miR-223 could decrease trastuzumab sensitivity of gastric cancer through suppressing expression of FBXW7 [156].…”