Table 5 Potential cardiokines and microRNA for the promotion of tumor progression

Serpin A3

In vitro studies

Colon cancer cells (HT-29) + SerpinA3/10 ng/mL

–

–

↑

–

–

SerpinA3 enhanced colon cancer cell proliferation

[16]

Colon cancer cells with high metastatic potential (HT-29LMM, KM-12L4)

↑ (vs low metastatic)

–

–

–

–

SerpinA3 expression was higher in colon cancer cells with higher metastatic potential and associated with colon cancer cell migration and invasion

[34]

HT-29LMM, KM-12L4 + downregulated SerpinA3

↓

–

–

↓

–

Breast cancer cells (MDA-MB-231, BT549, MCF-7, T-47D) + upregulated SerpinA3

↑

–

↑

↑

–

SerpinA3 enhanced breast cancer cell invasion and migration

[35]

MDA-MB-436 + downregulated SerpinA3

↓

–

↓

↓

–

Lung adenocarcinoma cells (CADO-LC11, LC29, LC45)

↑

–

–

–

–

SerpinA3 expression was increased in lung adenocarcinoma cells

[33]

Lung non-adenocarcinoma cells (OC-35, OC-10, CADO-LC22, CADO-LC3, CADO-LC15)

↔

–

–

–

–

GBM cells (U251MG) + downregulated SerpinA3

↓

–

–

↓

–

SerpinA3 enhanced GBM cell invasion

[36]

In vivo studies

MI-induced HF APC^min mice

–

–

↑

–

–

Increased SerpinA3 cardiac expression in MI-induced HF was associated with increased tumor growth in APC^min mice model

[16]

Heterotopic heart transplant of MI heart in APC^min mice into APC^min mice

–

–

↑

–

–

ATF3-transgenic mice with PyMT

↔

–

↑

–

–

Cardiac remodeling in ATF3-transgenic mice did not increase SerpinA3 expression, but enhanced breast cancer growth

[24]

Low-dose PE induced hypertension mice with PyMT

↔

–

↑

–

–

Cardiac remodeling without LV systolic dysfunction did not increase Serpin A3 expression, but enhanced breast cancer growth

[25]

Mice + downregulated SerpinA3 colon cancer cells (HT-29LMM)

↓

–

–

↓

–

SerpinA3 regulated liver metastasis of colon cancer in a mouse model

[34]

Clinical studies

Colon cancer patients

↑ (vs negative)

–

↔

↑

–

Increased SerpinA3 expression in colon cancer tissue was associated with metastasis

[34]

Lung cancer patients

↑ (vs negative)

–

↑

↔

↓

Increased SerpinA3 expression in lung cancer tissue was associated with larger tumor size and poor survival

[33]

Lung cancer patients

–

↑

–

↑

–

Plasma SerpinA3 levels was increased in lung cancer patients and associated with metastasis

[38]

Breast cancer patients

↑

–

–

–

–

SerpinA3 expression was increased in breast cancer tissue

[35]

Glioma patients

↑

–

–

–

↓

SerpinA3 expression was increased in brain glioma tissue and associated with poor survival

[36]

Serpin A1

In vitro studies

Colon cancer cells (HT-29) + SerpinA1/50 ng/mL

–

–

↑

–

–

SerpinA1 enhanced colon cancer cell proliferation

[16]

Gastric cancer cells (AGS, MKN45) + upregulated SerpinA1

↑

–

–

↑

–

SerpinA1 promoted gastric cancer cell migration and invasion

[44]

AGS, MKN45 + downregulated SerpinA1

↓

–

–

↓

–

Colon cancer cells (DLD-1, SW-480) + upregulated SerpinA1

↑

–

–

↑

–

SerpinA1 promoted colon, breast and ovarian cancer cell invasion and migration

[42]

DLD-1, SW-480 + downregulated SerpinA1

↓

–

–

↓

–

Breast cancer cell (MCF-7, MDA-MB-231) + upregulated SerpinA1

↑

–

–

↑

–

MCF-7, MDA-MB-231 + downregulated SerpinA1

↓

–

–

↓

–

Ovarian cancer cells (A2780, SKVO3) + upregulated SerpinA1

↑

–

–

↑

–

A2780, SKVO3 + downregulated SerpinA1

↓

–

–

↓

–

Lung adenocarcinoma cell with high metastatic potential (CL1-5)

↑ (vs low metastatic CL1-0)

–

–

–

–

SerpinA1 expression was higher in lung adenocarcinoma cells with higher metastatic potential and associated with cell migration and invasion

[43]

CL1-5 + downregulated SerpinA1

↓

–

–

↓

–

CL1-0 + upregulated SerpinA1

↑

–

–

↑

–

Lung adenocarcinoma cells (A549, SPC-A1) + upregulated SerpinA1

↑

–

–

↑

–

SerpinA1 promoted lung cancer cell migration

[45]

A549, SPC-A1 + downregulated SerpinA1

↓

–

–

↓

–

NSCLC cells (H661) + upregulated SerpinA1

↑

–

↑

↑

–

SerpinA1 promoted NSCLC cell proliferation and migration

[41]

NSCLC cells (H1975) + downregulated SerpinA1

↓

–

↓

↓

–

In vivo study

Mice + lung adenocarcinoma cells (CL1-5)

↑

–

–

↑

–

SerpinA1 promoted lung metastasis in lung adenocarcinoma mice

[43]

Mice + downregulated SerpinA1 CL1-5

↓

–

–

↔

–

Clinical studies

Gastric cancer patients

↑ (vs negative)

–

↑

↑

↓

SerpinA1 expression was associated with tumor size, lymph node metastasis and poor survival in gastric cancer patients

[44]

Colorectal cancer patients

↑ (vs negative)

–

↑

↑

↓

SerpinA1 expression was associated with tumor size, metastasis and poor survival in colorectal cancer patients

[42]

Lung adenocarcinoma patients

↑(vs negative)

–

↔

↑

↓

SerpinA1 expression was associated with lymph node metastasis and poor survival in lung adenocarcinoma patients

[43, 45]

NSCLC patients

↓

–

–

–

↓

SerpinA1 expression was decreased in NSCLC tumor tissue and was associated with poor survival

[41]

Periostin

In vitro studies

Breast cancer cells (PyMT) + Periostin 2000–4000 ng/mL/48 h

–

–

↑

–

–

Periostin enhanced breast and lung cancer cell proliferation

[23]

PyMT + Periostin 1000 ng/mL/48 h

–

–

↔

–

–

Lung cancer cells (LLC) + Periostin 2000–4000 ng/mL/48 h

–

–

↑

–

–

LLC + Periostin 1000 ng/mL/48 h

–

–

↔

–

–

Colon cancer cells (CX-1NS) in serum depleted condition + upregulated periostin

↑

–

–

–

–

Periostin promoted colon cancer cell survival in conditions of stress

[58]

Breast cancer cells (MCF-7) + upregulated periostin

↑

–

–

–

–

Periostin promoted angiogenesis in breast cancer cells

[57]

NSCLC cells (A549) + upregulated periostin

↑

–

↑

↑

–

Periostin enhanced NSCLC cell proliferation and migration

[56]

In vivo studies

Mice + upregulated periostin colon cancer cells (CX-1NS)

↑

–

–

↑

–

Periostin enhanced colon cancer growth and metastasis in mouse model

[58]

SCID mice + upregulated periostin breast cancer cells (MDA-MB-231)

↑

–

↑

–

–

Periostin enhanced breast cancer growth in an SCID mouse model

[57]

Clinical studies

Colon cancer patients

↑

↑

–

↑

↓

Plasma periostin and tumor expression were increased in colon cancer and associated with metastasis and poor survival

[58, 59]

Breast cancer patients

↑

–

↔

↔

↓

Tumor periostin expression was increased in breast cancer and associated with poor survival

[57, 60]

Breast cancer patients

–

↑

↔

↑

–

Plasma periostin level was higher in breast cancer with bone metastasis

[66]

NSCLC patients

↑

↑

↔

↔

↓

Plasma periostin level and tumor expression were elevated in NSCLC patients and associated with poor survival

[56, 64]

HCC patients

↑ (vs low level)

–

↔

↑

↓

Higher periostin expression in HCC was associated with metastasis and poor survival

[62]

HCC patients

–

↑

↔

↔

↓

Plasma periostin level was increased in HCC patients and associated with poor survival

[65]

Prostate cancer patients

↑

–

–

↑

↓

Tumor periostin expression was increased in prostate cancer and associated with advanced stages and poor survival

[61, 63]

miR-21

In vitro studies

Colorectal cancer cells (HCT-116, SW480) + upregulated miR-21

↑

–

↑

↑

–

miR-21 promoted colorectal cancer cell proliferation and invasion

[78]

HCT-116, SW480 + downregulated miR-21

↓

–

↓

↓

–

Colorectal cancer cells (RKO) + downregulated miR-21

↓

–

–

↓

–

miR-21 promoted colorectal cancer cell invasion and metastasis

[81]

Breast cancer cells (BCAP-37, MCF-7, MDA-MB-231, MDA-MB-435)

↑

–

–

–

–

miR-21 increased expression in breast cancer cells and associated with cancer invasiveness

[82]

MDA-231 + upregulated miR-21

↑

–

–

↑

–

MDA-231 + downregulated miR-21

↓

–

–

↓

–

MDA-435 + downregulated miR-21

↓

–

–

↓

–

MCF-7 + upregulated miR-21

↑

–

–

↑

–

miR-21 promoted breast cancer cell invasion and migration

[83]

NSCLC cells (H2170, A549, SPC-A1)

↑

–

–

–

–

miR-21 expression was increased in NSCLC cells and associated with proliferation, migration and invasion

[79]

A549, H2170 + upregulated miR-21

↑

–

↑

↑

–

A549, H2170 + downregulated miR-21

↓

–

↓

↓

–

Gastric cancer cells (BGC-823) + upregulated miR-21

↑

–

↑

↑

–

miR-21 promoted gastric cancer cell growth and invasion

[80]

BGC-823 + downregulated miR-21

↓

–

↓

↓

–

Glioblastoma cells (A172, U87, U373, LN229, LN428, LN308)

↑

–

–

–

–

miR-21 expression was increased in glioblastoma cell lines

[84]

Glioblastoma cells (A172, U87) + downregulated miR-21

↓

–

–

↓

–

miR-21 enhanced glioblastoma cell invasion

[85]

HCC cells (HepG2, SK-HEP-1, SNU182, SNU449, PLC/PRF-5)

↑

–

–

↑

–

miR-21 expression was increased in HCC cells and associated with invasiveness

[86]

HepG2, SK-HEP-1, SNU182, PLC/PRF-5 + downregulated miR-21

↓

–

–

↓

–

DLBCL cells (CRL-2630)

↑

–

–

–

–

miR-21 expression was increased in DLBCL cells

[87]

In vivo studies

Mice + upregulated miR-21 colon cancer cells (HCT-116)

↑

–

↑

–

–

miR-21 promoted colorectal cancer growth in mouse model

[78]

Mice + downregulated miR-21 HCT-116

↓

–

↓

–

–

Mice + downregulated miR-21 breast cancer cells (MCF-7)

↓

–

↓

–

–

miR-21 promoted breast cancer growth in mouse model

[83]

Clinical studies

Colorectal cancer patients

↑

–

–

↑

–

miR-21 expression was increased in colorectal cancer and associated with metastasis

[78]

Colon cancer patients

↑

–

–

–

↓

miR-21 expression was increased in colon cancer and associated with poor survival in colon cancer patients

[89]

Breast cancer patients

↑

–

–

↑

–

miR-21 expression was increased in breast cancer and associated with metastasis

[82, 88]

Breast cancer patients

–

↑

–

–

–

Plasma miR-21 levels were increased in breast cancer patients

[83]

NSCLC patients

–

↑

–

↑

↓

Plasma miR-21 level was increased in NSCLC patients and associated with lymph node metastasis and poor survival

[90]

NSCLC patients

↑

–

–

↑

–

Tumor miR-21 expression was increased in NSCLC and associated with lymph node metastasis

[79]

Lung cancer patients

↑

–

–

–

–

Tumor miR-21 expression was increased in lung cancer tissue

[88]

Prostate cancer patients

↑

–

–

–

–

Tumor miR-21 expression was increased in prostate cancer tissue

[88]

Prostate cancer patients

–

↑

–

↑

–

Plasma miR-21 level was increased in prostate cancer patients and associated with metastasis

[92]

Gastric cancer patients

–

↑

–

–

–

Plasma miR-21 level was increased in gastric cancer patients

[91]

Gastric cancer patients

↑

–

–

↑

–

Tumor miR-21 expression was increased in gastric cancer and associated with lymph node metastasis

[80]

Glioma patients

↑

–

–

–

–

Tumor miR-21 expression was increased in glioma

[85]

HCC patients

↑

–

–

–

–

Tumor miR-21 expression was increased in HCC

[86]

DLBCL patients

↑

–

–

–

–

Tumor miR-21 expression was increased in DLBCL

[87]

miR-22

In vitro studies

NSCLC cells (A549, H1299)

↓

–

–

–

–

miR-22 expression was decreased in NSCLC cell lines and suppressed cancer cell proliferation and migration

[102]

A549, H1299 + Overexpressed miR-22

↑

–

↓

↓

–

NSCLC cells (H1975, H1299) + transfected miR-22-3p

↑

–

↓

–

–

miR-22-3p inhibited NSCLC cell proliferation

[105]

H1975, H1299 + miR-22-3p inhibitor

↓

–

↑

–

–

Colorectal cancer cells (SW480, SW620, Caco2, HT29, LOVO, HCT15, HCT116)

↓

–

–

–

–

miR-22 expression was decreased in colorectal cancer cell lines and decreased proliferation and migration of colon cancer cells

[104]

SW480 + Overexpressed miR-22

↑

–

↓

↓

–

SW480 + miR-22 inhibitor

↓

–

↑

↑

–

HCC cells (Hep3B, SMMC7721)

↓

–

–

–

–

miR-22 expression was decreased in HCC cell lines and suppressed tumor cell proliferation

[103]

Hep3B, SMMC7721 + transfected with miR-22

↑

–

↓

–

–

Triple negative breast cancer cells (MDA-MB-231, MDA-MB-436, BT-20)

↓

–

–

–

–

miR-22-3p expression was decreased in triple negative breast cancer cells and suppressed cell proliferation and migration

[106]

MDA-MB-231, MDA-MB-436 + transfected with miR-22-3p

↑

–

↓

↓

–

Highly metastatic breast cancer cells (MDA-MB-231, Hs578T)

↑ (vs low metastatic MCF7, T47D)

–

–

–

–

miR-22 expression was higher in highly metastatic breast cancer cell lines and increased cell migration and invasion

[107]

MDA-MB-231 + miR-22 inhibitor

↓

–

–

↓

–

MCF7 + overexpressed miR-22

↑

–

–

↑

–

Prostate cancer cells (Ca-HpV-10, DU145, PC3, VCap)

↑

–

–

–

–

miR-22 expression was increased in prostate cancer cell lines

[108]

In vivo studies

Mice + Overexpressed miR-22 in NSCLC cells (A549)

↑

–

↓

–

–

miR-22 suppressed lung cancer growth in mice

[102]

Xenograft colorectal cancer mice + overexpressed miR-22 colorectal cancer cells (SW480)

↑

–

↓

–

–

Overexpression of miR-22 inhibited colorectal cancer growth

[104]

Mice + overexpressed miR-22 in HCC cells (Hep3B/SMMC7721)

↑

–

↓

–

–

miR-22 suppressed HCC growth in mice

[103]

Orthotopic immunodeficient mice + overexpressed miR-22 in breast cancer cells (MCF-7)

↑

–

–

↑

–

miR-22 enhanced breast cancer cell metastasis

[112]

MMTV-miR-22 transgenic mice

↑

–

↑

↑

–

miR-22 promoted breast cancer growth and distant metastasis

Orthotopic breast cancer mice (MDA-MB-231, MDA-MB-436) + miR-22-3p

↑

–

↓

–

–

miR-22-3p suppressed breast cancer proliferation

[106]

Mice + overexpressed miR-22 in prostate cancer cells (DU145)

↑

–

↑

–

–

miR-22 promoted prostate cancer growth

[108]

Clinical studies

NSCLC patients

↓

–

–

–

–

Tumor miR-22-3p expression was decreased in NSCLC patients

[105]

Lung cancer patients

↓

–

–

–

–

Tumor miR-22-3p expression was decreased in lung cancer patients

[102]

Advanced NSCLC patients

–

↑

–

–

–

Plasma miR-22 level was increased in advanced NSCLC patients

[111]

Colorectal cancer patients

↓

–

–

↓

↑

Tumor miR-22 expression was decreased in colon cancer and low miR-22 expression was associated with poor survival and liver metastasis

[104, 109]

Colorectal cancer patients

–

↓

–

–

–

Plasma miR-22-3p level was decreased in colorectal cancer patients

[113]

Colon cancer patients

↑

–

–

–

–

Tumor miR-22-3p expression was increased in colon cancer patients

[110]

HCC patients

↓

–

–

–

↑

Tumor miR-22 expression was decreased in HCC and low miR-22 expression was associated with poor survival

[103]

Triple negative breast cancer patients

↓

–

–

–

–

Tumor miR-22-3p expression was decreased in triple negative breast cancer patients

[106]

Breast cancer patients

↑ (vs low level)

–

–

–

↓

Elevated tumor miR-22 expression was associated with poor survival in breast cancer patients

[107]

Prostate cancer patients

↑

–

–

–

–

Tumor miR-22 expression was increased in prostate cancer patients

[108]

Pancreatic cancer patients

–

↑

–

–

–

Plasma miR-22-3p level was increased in pancreatic cancer patients

[114]