The contrary functions of lncRNA HOTAIR/miR‐17‐5p/PTEN axis and Shenqifuzheng injection on chemosensitivity of gastric cancer cells

Abstract

This study was implemented to figure out whether lncRNA HOTAIR/miR‐17‐5p/PTEN axis played a role that was opposite to Shenqifuzheng (SQFZ) injection in regulating the chemosensitivity of gastric cancer cells. The gastric cancer tissues were gathered and four gastric cancer cell lines were prepared, including BGC‐823, MGC‐803, SGC‐7901, and MKN28. Moreover, cisplatin, adriamycin, mitomycin, and 5‐fluoroura were managed as the chemo‐therapeutics, and SQFZ was prepared as a Chinese medicine. Striking distinctions of HOTAIR, miR‐17‐5p, and PTEN expressions were observed between gastric cancer tissues and para‐carcinoma normal tissues (P < 0.05). MKN28 was associated with the highest resistance to cisplatin, adriamycin, mitomycin, and 5‐fluoroura among all the cell types, and SQFZ significantly improved the MKN28 cells’ sensitivity to the drugs (P < 0.05). The over‐expressed HOTAIR and miR‐17‐5p, as well as under‐expressed PTEN tended to significantly facilitate the viability, EMT process and proliferation of MKN28 cells that were subject to treatment of chemo‐therapies (P < 0.05). SQFZ could amplify the effects of si‐HOTAIR, miR‐17‐5p inhibitor, and pcDNA‐PTEN on boosting the chemosensitivity of gastric cancer cells (P < 0.05). In addition, HOTAIR was also found to directly target miR‐17‐5p, and PTEN appeared to be subject to the modification of HOTAIR and miR‐17‐5p in its acting on the viability, proliferation, EMT process, and apoptosis of gastric cancer cells. The HOTAIR/miR‐17‐5p/PTEN axis could be regarded as the potential treatment targets for gastric cancer, and adjuvant therapy of SQFZ injection could assist in further improving the treatment efficacy of chemo‐therapies for gastric cancer.

MSC-induced lncRNA HCP5 drove fatty acid oxidation through miR-3619-5p/AMPK/PGC1α/CEBPB axis to promote stemness and chemo-resistance of gastric cancer

“…HCP5 interacted with miR-3619-5p to regulate stemness and chemo-resistance in GC Next, regulatory mechanism of HCP5 in GC was explored. As widely reported, lncRNAs can function as miRNA sponge to regulate chemo-resistance in cancer cells 36,37 . Therefore, we searched for the target miRNAs for HCP5.…”

“…LncRNAs are demonstrated to pose significant effects on the cancer-related metabolism, such as lipid metabolism and glycolysis, in a variety of cancer types 39,40 . Also, accumulating studies have attributed the development of chemo-resistance to aberrant expression of certain lncRNAs 37,38 . These discoveries suggested that MSCs might regulate chemoresistance in GC through altering expressions of lncRNAs, specifically the lncRNAs related to metabolic pathways.…”

“…Long non-coding RNAs (lncRNAs), a series of RNA transcripts without functional protein products 33,34 , are tightly linked to cancer-related metabolism and chemoresistance 35,36 . For example, the HOTAIR/miR-17-5p/ PTEN axis regulates the chemo-sensitivity in GC 37 . Knockdown of HULC facilitates apoptosis and alleviates chemo-resistance in GC 38 .…”

MicroRNA in Gastric Cancer Development: Mechanisms and Biomarkers

“…Several microRNAs associated with chemoresistance are also involved in invasion and migration; thus, they are also important for metastasis [83,100,101,105,106,[109][110][111][112][113]120]. Some of microRNAs were involved in both metastasis and chemoresistance, as shown in Figure 2.…”

“…By inhibiting PTEN, these microRNAs activate the PI3K/AKT/mTOR pathway and suppress apoptosis. A decrease in the expression of miR-17-5p and miR-147 inhibited proliferation, induced apoptosis, and increased the sensitivity of GC cells to chemotherapy [99,100]. A decrease in miR-193-3p expression inhibited proliferation and migration, and also increased the sensitivity of GC cells to 5-Fluorouracil (5-FU) in vitro and tumor growth in vivo [101].…”