Table I.
Expression and functional mechanisms of H19 in different types of cancer.
| Cancer type | Expression level | Mechanisms | (Refs.) |
|---|---|---|---|
| Lung cancer | Increased | i) H19 depresses miR-196b to elevate LIN28B; ii) H19 serves as a ceRNA and attaches miR-17 to modulate STAT3 expression; induces iii) H19 promotes EMT by downregulating miR-484; iv) H19 cisplatin resistance in patients | (81–84) |
| Gastric cancer | Increased | i) H19 functions as a ceRNA to regulate HER2 expression by suppressing let-7c expression; ii) H19-PEG10/IGF2BP3 axis promotes EMT in gastric cancer; iii) H19/miR-675 axis inhibits the expression of FADD and the downregulation of FADD inhibits the caspase cleavage cascades including caspase 8 and caspase 3 | (13,85,86) |
| Pancreatic cancer | Increased | i) H19/miR-675/E2F-1 regulatory loop affects the cell cycle; ii) H19 increases HMGA2-mediated EMT through antagonizing let-7 | (14,87) |
| Liver cancer | Increased | i) H19 targets miR-193a-3p and regulates PSEN1 expression, which influences the survival rates and proliferative abilities of HCC cells; ii) aberrant TGF-β/H19 signaling axis via Sox2 in TICs that regulates hepatocarcinogenesis; iii) abnormal regulation of H19 results in biallelic expression of IGF2, leading to exceptional cell proliferation | (15,88,89) |
| Colorectal cancer | Increased | i) Overexpression of H19 activates the RAS-MAPK signaling pathway, promoting invasion and metastasis of colorectal cancer; ii) H19 induces the EMT process in colon cancer cells; iii) H19 sponges miR-138 to upregulate the expression of HMGA1, enhancing the invasion and migration of colon cancer; iv) H19 competitively binds to miR-200a and depresses the expression of β-catenin in colorectal cancer | (90–93) |
| Endometrial cancer | Increased | i) Overexpression of H19 regulates the expression of HOXA10 via targeting miR-612, promoting cell proliferation of endometrial cancer; ii) H19 modulates EMT process, reinforcing the aggressiveness of endometrial cancer; iii) H19 acts as a sponge to bind let-7, leading to high expression of IGF1R and therefore promotes endometrial stromal hyperplasia | (94–96) |
| Breast cancer | Increased | i) H19 derives miR-675 and contributes to the development of breast cancer; ii) H19 functions as a ceRNA of various miRNAs and regulates the expression of corresponding target genes; iii) association between MYC and H19 plays an important role in the progression of breast cancer | (20–44,53–58) |
| Bladder cancer | Increased | i) High expression of H19 inhibits E-cadherin expression and strengthens metastasis of bladder cancer; ii) H19 acts as a ceRNA to sponge miR-29b-3p and promotes the expression of DNMT3B, resulting in metastasis and EMT of bladder cancer; iii) H19 increases miR-675 expression, which can inhibit the activation of p53 and reduce the expression of Bax/Bcl-2 and cyclin D1, leading to bladder cancer cell proliferation; iv) H19 increases the expression of ID2 and promotes bladder cancer growth | (97–100) |
| Prostate cancer | Decreased/increased | i) H19 and miR-675 is significantly downregulated in metastatic prostate cancer cells. miR-675 binds with 3′UTR of TGFBI mRNA and decreases the translation of TGFBI; ii) High expression of H19 is associated with the process of neuroendocrine transdifferentiation (NEtD) in prostate cancer | (101–102) |
miR, microRNA; ceRNA, competing endogenous RNA; EMT, epithelial-to-mesenchymal transition; HER2, human epidermal growth factor receptor 2; FADD, fas-associated via death domain; HMG, high-mobility group; PSEN1, presenilin-1; HCC, hepatocellular carcinoma; TGF-β, tumor growth factor-β; TICs, tumor-initiating hepatocytes; IGF2, insulin-like growth factor 2; RAS, rat sarcoma; MAPK, mitogen-activated protein kinase; DNMT3B, DNA-methylase 3β; ID2, inhibitor of DNA binding/differentiation 2; 3′UTR, 3′untranslated region; NEtD, neuroendocrine transdifferentiation.