MicroRNA-148a inhibits the proliferation and promotes the paclitaxel-induced apoptosis of ovarian cancer cells by targeting PDIA3

Abstract

MicroRNAs (miRs) are a class of non-coding RNAs that function as key regulators of gene expression at the post-transcriptional level. miR-148a has been suggested to be associated with human ovarian cancer, however, the detailed functions of miR‑148a in ovarian cancer remain to be fully elucidated. The present study aimed to investigate the regulatory mechanism of miR-148a in ovarian cancer cells. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were conducted to examine the RNA and protein levels, respectively. The luciferase reporter assay was used to determine the target relationship. Cell proliferation and apoptosis assays were additionally conducted. The present study demonstrated that miR‑148a inhibited cell proliferation and promoted the paclitaxel‑induced apoptosis of ovarian cancer cells. Furthermore, protein disulfide isomerase family A, member 3 (PDIA3) was identified as a target gene of miR‑148a. A fluorescent reporter assay was performed to confirm that miR‑148a was able to directly bind to the 3'‑untranslated region of PDIA3 mRNA. In addition, miR‑148a was frequently downregulated in ovarian cancer tissue, whereas the expression levels of PDIA3 were increased. Knockdown of PDIA3 significantly inhibited the proliferation and promoted the paclitaxel‑induced apoptosis of the ovarian cancer cells, whereas overexpression of PDIA3 had the opposite effects. Therefore, the results of the present study suggested that miR‑148a inhibited the proliferation and promoted the paclitaxel‑induced apoptosis of ovarian cancer cells, and this may be partly attributed to direct targeting of PDIA3.

MicroRNA-148a inhibits migration of breast cancer cells by targeting MMP-13

“…In multiple types of tumors, such as ovarian cancer, miR148a acts as a tumor suppressor to inhibit the growth of cancer cells [12,28,29]. However, a number of studies argue that miR-148a acts as an oncomiR or tumor suppressor depending on the tumor types.…”

A secretome profile indicative of oleate-induced proliferation of HepG2 hepatocellular carcinoma cells

“…A number of previous studies have shown associations of the proteins selected in this study, especially the four upregulated proteins (MIF, THBS1, PDIA3, and APOA1), with various features of cancer pathophysiology in liver cancer, as well as other types of cancers (Supplementary Table S7 ): (1) MIF was reported to be increased at both the mRNA and protein levels in liver cancer tissues compared to noncancerous tissues 65 and to promote tumor survival, angiogenesis, and/or metastasis in colon, head and neck, liver, and/or prostate cancers; 65 – 68 (2) THBS1 was shown to be elevated in liver cancer 69 and to promote tumor survival, aggressiveness, angiogenesis, and metastasis in breast, bladder, liver, gastric, prostate, and/or pancreatic cancers; 69 – 74 (3) PDIA3 was reported to be elevated in liver cancer 75 and to enhance the proliferation of tumor cells, metastasis, and/or invasion in breast, colon, ovarian, and/or pancreatic cancers; 75 – 79 and (4) APOA1 was observed to be elevated in the serum of liver cancer patients 80 , as well as in the serum of breast, colon, and lung cancers 81 – 83 and in the urine of bladder cancer 84 , and its abundance showed positive correlations with aggressiveness and/or metastasis in bladder, colon, and lung cancers 82 , 85 , 86 . These data suggest that the secreted proteins with various tumors might serve as a secretome profile that can represent cancer pathophysiology, such as the proliferation of tumor cells.…”

miR-148a increases the sensitivity to cisplatin by targeting Rab14 in renal cancer cells

“…For example, ectopic expression of miR-148a sensitized the cells to TRAIL via the down-modulation of matrix metalloproteinase 15 (MMP15) and Rho-associated kinase 1 (ROCK1) in non-small cell lung cancer (22). In addition, enforced expression of miR-148a promotes paclitaxel-induced apoptosis of ovarian cancer cells by targeting PDIA3 (23). miR-148a was found to induce apoptosis and activate the caspase-dependent pathway, indicating that it might function as a tumor suppressor in renal cancer cells.…”