Hsa-let-7g miRNA regulates the anti-tumor effects of gastric cancer cells under oxidative stress through the expression of DDR genes

Abstract

-Oxidative stress is linked to increased risk of gastric cancer (GC). Recent reports have found that hsa-let-7g microRNA (miRNA) has properties of anti-tumor and resistance to damages induced by oxidized low-density lipoprotein (ox-LDL). Dysregulation of hsa-let-7g was present in GC in vivo and in vitro under exogenous stress. However, we didn't know whether there are regulatory mechanisms of hsa-let-7g in GC under oxidative stress. This study was aimed at investigating the effects of hsa-let-7g microRNA (miRNA) on GC under oxidative stress. The results showed that H 2 O 2 induced the increase of DNA damage response (DDR) genes (ATM, H2AX and Chk1) and downregulation of hsa-let-7g in GC cells. Further study confirmed Hsa-let-7g caused the apoptosis and loss of proliferation in GC cells exposed to H 2 O 2 associated with repression of DDR system. Yet, we found let-7g didn't target DDR genes (ATM, H2AX and Chk1) directly. In addition, data revealed hsa-let-7g miRNA increased the sensitivity of GC to X-rays involving in ATM regulation as well according to application of X-rays (another DDR inducer). In conclusion, Hsa-let-7g miRNA increased the sensitivity of GC to oxidative stress by repression activation of DDR indirectly. Let-7g improved the effects of X-rays on GC cells involving in DDR regulation as well.

Non-coding RNAs in Various Stages of Liver Disease Leading to Hepatocellular Carcinoma: Differential Expression of miRNAs, piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs

“…The Let-7 family has 10 members in the human genome (Let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, let-7i, miR-98, and miR-202 38 ), which are involved in gene regulation and cell adhesion. We found, Let-7f microRNAs were strikingly downregulated in HGDN and eHCC (1 million-fold change) and Let-7g in HCC (358-fold change) with similar reports published in gastric 39 , 40 , prostate 41 , colon 42 , 43 , small cell lung 44 , thyroid 45 , breast 46 , 47 , and hepatocellular cancer 48 , 49 . miR-221, was found to be upregulated in HCC via in silico analysis and has multiple known pathway targets, such as p27Kip1, p53, BMF, PI3K, PTEN, and mTOR 50 .…”

The MicroRNA hsa-let-7g Promotes Proliferation and Inhibits Apoptosis in Lung Cancer by Targeting HOXB1

“…11 The hsa-let-7g miRNA (also known as miR-let-7g and let-7g) is a member of the let-7 miRNA family that can exert vital biological effects in various diseases, including cancer. Hu, et al 12 reported that hsa-let-7g can exert anti-tumor effects in gastric cancer by inhibiting oncogenesis induced by oxidative stress. Another study indicated that hsa-let-7g could serve as an indicator for the prognosis of S-1-based chemotherapy.…”

Identification of recurrence-associated microRNAs in stage I lung adenocarcinoma

“…[ 25 ] In gastric cancer cells, let-7g was reported to induce sensitivity to oxidative stress by indirect repression of DNA damage responsive and served as a tumor suppressor gene. [ 26 ] In breast cancer tissues and cell lines, low expression of let-7g was associated with invasion and metastasis, further supporting its role as a tumor suppressor gene. [ 27 ] MiR-143 levels have been reported to be lower in bladder cancer tissue than normal tissue.…”